研究者紹介システム

田守 義和
タモリ ヨシカズ
大学院医学研究科 医科学専攻
教授
医学
Last Updated :2022/04/15

研究者情報

所属

  • 【主配置】

    大学院医学研究科 医科学専攻

学位

  • 博士(医学), 神戸大学

ジャンル

  • 医療・健康 / 臨床医学

コメントテーマ

  • 糖尿病
  • 肥満
  • 生活習慣病
  • インスリン抵抗性
  • 脂肪細胞

研究ニュース

研究活動

研究キーワード

  • 肥満
  • インスリン抵抗性
  • 2型糖尿病

研究分野

  • ライフサイエンス / 代謝、内分泌学

委員歴

  • 日本糖尿病学会, 学術評議員
  • 日本病態栄養学会, 学術評議員
  • 日本肥満学会, 評議員
  • 日本内分泌学会, 評議員

論文

  • Natsu Otowa-Suematsu, Kazuhiko Sakaguchi, Akihiro Kaneko, Jun Ito, Yasuko Morita, Hiroshi Miura, Tomoko Yamada, Anna So, Hisako Komada, Yuko Okada, Yushi Hirota, Yoshikazu Tamori, Wataru Ogawa

    AIMS: Whereas homeostasis model assessment of insulin resistance (HOMA-IR), an easily measured but limited index of insulin resistance, has been shown to correlate with impairment of cardiac function in individuals without diabetes, the pathological relevance of insulin resistance to the development of cardiac dysfunction in individuals with type 2 diabetes has remained unclear. Here we investigated the relation between left ventricular (LV) function as assessed by echocardiography and insulin resistance as evaluated by hyperinsulinemic-euglycemic clamp analysis, the gold standard for measurement of this parameter, in individuals with type 2 diabetes. METHODS: This retrospective study included 34 individuals with type 2 diabetes who underwent both hyperinsulinemic-euglycemic clamp analysis and echocardiography. Both the insulin sensitivity index (ISI) as determined by glucose clamp analysis as well as HOMA-IR were determined as measures of insulin resistance. The ratio of the peak early- to late-diastolic mitral inflow velocities (E/A) and the LV ejection fraction (LVEF) were determined as measures of diastolic and systolic function, respectively. RESULTS: The ISI was significantly correlated with both the E/A ratio and LVEF (correlation coefficients of 0.480 and 0.360, respectively), whereas HOMA-IR was not correlated with either cardiac parameter. Multivariate analysis revealed that ISI was an independent predictor for both a high log [E/A] (P = 0.031) and a high LVEF (P = 0.045). CONCLUSIONS: Insulin resistance as evaluated by hyperinsulinemic-euglycemic clamp analysis may be causally related to LV diastolic and systolic dysfunction in individuals with type 2 diabetes.

    2021年06月03日, Journal of diabetes investigation, 英語, 国内誌

    研究論文(学術雑誌)

  • Tomoko Yamada, Kazuhiko Sakaguchi, Yuko Okada, Hiroshi Miura, Natsu Otowa-Suematsu, Anna So, Hisako Komada, Yushi Hirota, Takeshi Ohara, Yasuo Kuroki, Kenta Hara, Tomokazu Matsuda, Minoru Kishi, Akihiko Takeda, Kazuki Yokota, Yoshikazu Tamori, Wataru Ogawa

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors often increase the hematocrit. It remains unclear whether this increase would be observed in all patients administered SGLT2 inhibitors, however. We therefore used the data from the previous study and investigated time-dependent alterations of various outcomes related to erythrocytes, erythropoiesis, and clinical outcome in type 2 diabetes subjects (n = 89) treated with ipragliflozin for 16 weeks. Among a total of 89 participants, 71 subjects (80.0% of total participants) showed the elevation of the hematocrit and 18 subjects (20.0% of total participants) did not at 16 weeks. Although the hematocrit levels at baseline were significantly lower in hematocrit-elevated group than non-elevated group, they reached the same levels 4 weeks after the onset of treatment. Binomial logistic regression analysis demonstrated that a lower baseline hematocrit level was related to the elevation of hematocrit at 16 weeks. Optimal cutoff hematocrit levels at baseline to predict hematocrit elevation were 46.9% (male) and 41.7% (female) in ROC analysis. Random intercept model analysis revealed the serum erythropoietin level increased in both hematocrit-elevated and non-elevated groups, whereas only the former group showed an increase in the percentage of reticulocytes during the first 4 weeks. These results suggest that the ipragliflozin-induced increase in hematocrit which is affected by the baseline hematocrit level is attributable to the responsiveness to, but not to the production of, erythropoietin. Collectively, Ht elevation observed in administration of SGLT2 inhibitors can result from erythropoietin-induced erythropoiesis, which is determined by the pre-treatment Ht level. Trial registration: This trial has been registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR no. 000015478).

    2021年04月, Diabetology international, 12 (2), 197 - 206, 英語, 国内誌

    研究論文(学術雑誌)

  • Yuko Nabatame, Tetsuya Hosooka, Chikako Aoki, Yusei Hosokawa, Makoto Imamori, Yoshikazu Tamori, Yuko Okamatsu-Ogura, Takeshi Yoneshiro, Shingo Kajimura, Masayuki Saito, Wataru Ogawa

    AIMS/INTRODUCTION: Brown adipose tissue (BAT) utilizes large amounts of fuel for thermogenesis, but the mechanism by which fuel substrates are switched in response to changes in energy status is poorly understood. We have now investigated the role of Kruppel-like factor 15 (KLF15), a transcription factor expressed at a high level in adipose tissue, in the regulation of fuel utilization in BAT. MATERIALS AND METHODS: Depletion or overexpression of KLF15 in HB2 differentiated brown adipocytes was achieved by adenoviral infection. Glucose and fatty acid oxidation were measured with radioactive substrates, pyruvate dehydrogenase complex activity was determined with a colorimetric assay, and gene expression was examined by reverse transcription and real-time polymerase chain reaction analysis. RESULTS: Knockdown of KLF15 in HB2 cells attenuated fatty acid oxidation in association with downregulation of the expression of genes related to this process including Acox1 and Fatp1, whereas it increased glucose oxidation. Expression of the gene for pyruvate dehydrogenase kinase 4 (PDK4), a negative regulator of pyruvate dehydrogenase complex, was increased or decreased by KLF15 overexpression or knockdown, respectively, in HB2 cells, with these changes being accompanied by a respective decrease or increase in pyruvate dehydrogenase complex activity. Chromatin immunoprecipitation showed that Pdk4 is a direct target of KLF15 in HB2 cells. Finally, fasting increased expression of KLf15, Pdk4 and genes involved in fatty acid utilization in BAT of mice, whereas refeeding suppressed Klf15 and Pdk4 expression. CONCLUSIONS: Our results implicate KLF15 in the regulation of fuel switching between glucose and fatty acids in response to changes in energy status in BAT.

    2021年01月21日, Journal of diabetes investigation, 英語, 国内誌

    研究論文(学術雑誌)

  • Jun Ito, Munenobu Nogami, Yasuko Morita, Kazuhiko Sakaguchi, Hisako Komada, Yushi Hirota, Kenji Sugawara, Yoshikazu Tamori, Feibi Zeng, Takamichi Murakami, Wataru Ogawa

    Wiley, 2020年12月10日, Diabetes, Obesity and Metabolism

    研究論文(学術雑誌)

  • Hiroshi Miura, Kazuhiko Sakaguchi, Natsu Otowa-Suematsu, Tomoko Yamada, Anna So, Hisako Komada, Yuko Okada, Yushi Hirota, Yoshikazu Tamori, Wataru Ogawa

    To compare the effects of insulin degludec (IDeg) and insulin glargine U300 (IGlarU300) on glycaemic stability in subjects with type 1 diabetes. MATERIALS AND METHODS: In this multicentre, crossover trial, 46 individuals with type 1 diabetes and essentially undetectable circulating C-peptide were randomly assigned to either the IDeg-first/IGlarU300-second group or the IGlarU300-first/IDeg-second group, and were treated with the respective basal insulins for 4-week periods. Data were collected in the last week of each treatment period. The primary aim was to examine the potential non-inferiority of IDeg relative to IGlarU300 with regard to day-to-day variability, as evaluated by the standard deviation (SD) of fasting blood glucose (FBG) levels. Intra-day glycaemic variability and other variables were also determined by continuous glucose monitoring (CGM). RESULTS: The SD of FBG for IDeg was non-inferior to that for IGlarU300. The mean of FBG, coefficient of variation of FBG, and various glycaemic variability indexes determined by CGM did not differ between the two insulins. Whereas the administered doses of the insulins also did not differ, the mean glycaemic value was lower for IDeg than IGlarU300; the time above the target range (>180 mg/dL [10.0 mmol/L]) and the time below the target range (<70 mg/dL [3.9 mmol/L]) were shorter and longer, respectively, for IDeg than IGlarU300. CONCLUSIONS: Our data suggest that IDeg and IGlarU300 have comparable glucose-stabilizing effects in individuals with type 1 diabetes. However, the glucose-lowering effect of IDeg may be greater than that of IGlarU300 when titrated with a unit-based protocol.

    2020年12月, Diabetes, obesity & metabolism, 22 (12), 2356 - 2363, 英語, 国際誌

    研究論文(学術雑誌)

  • Morita Y, Nogami M, Sakaguchi K, Okada Y, Hirota Y, Sugawara K, Tamori Y, Zeng F, Murakami T, Ogawa W

    OBJECTIVE: Positron emission tomography (PET)-computed tomography has revealed that metformin promotes the intestinal accumulation of [18F]fluorodeoxyglucose (FDG), a nonmetabolizable glucose derivative. It has remained unknown, however, whether this accumulation occurs in the wall or intraluminal space of the intestine. We here addressed this question with the use of [18F]FDG PET-MRI, a recently developed imaging method with increased accuracy of registration and high soft-tissue contrast. RESEARCH DESIGN AND METHODS: Among 244 individuals with type 2 diabetes who underwent PET-MRI, we extracted 24 pairs of subjects matched for age, BMI, and HbA1c level who were receiving treatment with metformin (metformin group) or were not (control group). We evaluated accumulation of [18F]FDG in different portions of the intestine with both a visual scale and measurement of maximum standardized uptake value (SUVmax), and such accumulation within the intestinal wall or lumen was discriminated on the basis of SUVmax. RESULTS: SUVmax of the jejunum, ileum, and right or left hemicolon was greater in the metformin group than in the control group. [18F]FDG accumulation in the ileum and right or left hemicolon, as assessed with the visual scale, was also greater in the metformin group. SUVmax for the intraluminal space of the ileum and right or left hemicolon, but not that for the intestinal wall, was greater in the metformin group than in the control group. CONCLUSIONS: Metformin treatment was associated with increased accumulation of [18F]FDG in the intraluminal space of the intestine, suggesting that this drug promotes the transport of glucose from the circulation into stool.

    2020年07月, Diabetes Care, 43 (7), 1 - 7, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Tetsuya Hosooka, Yusei Hosokawa, Kaku Matsugi, Masakazu Shinohara, Yoko Senga, Yoshikazu Tamori, Chikako Aoki, Sho Matsui, Tsutomu Sasaki, Tadahiro Kitamura, Masashi Kuroda, Hiroshi Sakaue, Kazuhiro Nomura, Kei Yoshino, Yuko Nabatame, Yoshito Itoh, Kanji Yamaguchi, Yoshitake Hayashi, Jun Nakae, Domenico Accili, Takehiko Yokomizo, Susumu Seino, Masato Kasuga, Wataru Ogawa

    Although adipocytes are major targets of insulin, the influence of impaired insulin action in adipocytes on metabolic homeostasis remains unclear. We here show that adipocyte-specific PDK1 (3'-phosphoinositide-dependent kinase 1)-deficient (A-PDK1KO) mice manifest impaired metabolic actions of insulin in adipose tissue and reduction of adipose tissue mass. A-PDK1KO mice developed insulin resistance, glucose intolerance, and hepatic steatosis, and this phenotype was suppressed by additional ablation of FoxO1 specifically in adipocytes (A-PDK1/FoxO1KO mice) without an effect on adipose tissue mass. Neither circulating levels of adiponectin and leptin nor inflammatory markers in adipose tissue differed between A-PDK1KO and A-PDK1/FoxO1KO mice. Lipidomics and microarray analyses revealed that leukotriene B4 (LTB4) levels in plasma and in adipose tissue as well as the expression of 5-lipoxygenase (5-LO) in adipose tissue were increased and restored in A-PDK1KO mice and A-PDK1/FoxO1KO mice, respectively. Genetic deletion of the LTB4 receptor BLT1 as well as pharmacological intervention to 5-LO or BLT1 ameliorated insulin resistance in A-PDK1KO mice. Furthermore, insulin was found to inhibit LTB4 production through down-regulation of 5-LO expression via the PDK1-FoxO1 pathway in isolated adipocytes. Our results indicate that insulin signaling in adipocytes negatively regulates the production of LTB4 via the PDK1-FoxO1 pathway and thereby maintains systemic insulin sensitivity.

    2020年05月11日, Proceedings of the National Academy of Sciences of the United States of America, 117 (21), 11674 - 11684, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Anna So, Kazuhiko Sakaguchi, Yuko Okada, Yasuko Morita, Tomoko Yamada, Hiroshi Miura, Natsu Otowa-Suematsu, Tomoaki Nakamura, Hisako Komada, Yushi Hirota, Yoshikazu Tamori, Wataru Ogawa

    We had aimed to determine whether homeostasis model assessment-insulin resistance (HOMA-IR) reflects insulin resistance-sensitivity during treatment with a sodium-glucose cotransporter 2 inhibitor (SGLT2i). Hyperinsulinemic-euglycemic clamp analysis was performed in 22 patients with type 2 diabetic patients taking dapagliflozin (5 mg/day before or after breakfast). Propensity score matching of these individuals (SGLT2i group) for age, sex, body mass index, and clamp-derived tissue glucose uptake rate with 44 type 2 diabetic patients who had undergone clamp analysis without SGLT2i treatment (control group) identified 17 paired subjects in each group for further analysis of the relation between HOMA-IR and a clamp-derived insulin sensitivity index (ISI). Natural log-transformed HOMA-IR was negatively correlated with ISI in both SGLT2i (r = -0.527, p = 0.030) and control (r = -0.534, p = 0.027) groups. The simple regression lines for log-transformed HOMA-IR and ISI in the two groups showed similar slopes but differed in their intercepts. Multivariate analysis revealed that HOMA-IR for patients with the same ISI in the two groups was related by the formula: HOMA-IRcontrol = HOMA-IRSGLT2i × 2.45. In conclusion, HOMA-IR was well correlated with ISI during SGLT2i treatment, but values corresponding to the same ISI were lower in the SGLT2i group than in the control group.

    2020年02月06日, Endocrine journal, 67 (5), 501 - 507, 英語, 国内誌

    [査読有り]

    研究論文(学術雑誌)

  • Hiroshi Miura, Kazuhiko Sakaguchi, Yuko Okada, Tomoko Yamada, Natsu Otowa-Suematsu, Anna So, Hisako Komada, Yushi Hirota, Takeshi Ohara, Yasuo Kuroki, Kenta Hara, Tomokazu Matsuda, Minoru Kishi, Akihiko Takeda, Kazuki Yokota, Yoshikazu Tamori, Wataru Ogawa

    AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve blood glucose control, as well as reducing bodyweight by promoting urinary glucose excretion. The weight loss is less than expected from urinary glucose loss, however, likely because of an increase in food intake. To investigate whether SGLT-2 inhibitors might increase appetite by affecting related hormones, we examined the effects of the SGLT-2 inhibitor, ipragliflozin, including those on appetite-regulating hormones, in individuals with suboptimally controlled type 2 diabetes. MATERIALS AND METHODS: The present prospective, multicenter, open-label study was carried out with 96 patients with a body mass index of ≥22 kg/m2 who were treated with ipragliflozin (50 mg/day) for 16 weeks. Parameters including glycated hemoglobin level, bodyweight, circulating leptin and active ghrelin concentrations, and appetite as assessed with a visual analog scale were measured before and during treatment. RESULTS: Both glycated hemoglobin level (from 7.9 ± 0.8 to 7.1 ± 0.7%) and bodyweight (from 75.2 ± 12.6 to 72.6 ± 12.4 kg) were significantly decreased after treatment for 16 weeks. The fasting serum leptin level was significantly decreased after 2 weeks (from 19.5 ± 13.1 to 18.1 ± 12.4 ng/mL) and remained decreased up to 16 weeks, even after adjustment for bodyweight, whereas the plasma active ghrelin level showed no significant change. The visual analog scale score for hunger was significantly increased at 2 and 8 weeks. CONCLUSIONS: The present results suggest that ipragliflozin improved glycemic control and reduced bodyweight, but also reduced serum leptin levels and might thereby have increased appetite.

    2019年09月, Journal of diabetes investigation, 10 (5), 1254 - 1261, 英語, 国内誌

    [査読有り]

    研究論文(学術雑誌)

  • The Novel Lipid-Lowering Drug D-47 Ameliorates Hepatic Steatosis and Promotes Brown/Beige-Like Change of White Adipose Tissue in db/db Mice.

    Nao Mizusaki, Kazuhiro Nomura, Tetsuya Hosooka, Masashi Shiomi, Kazuo Ogawa, Tetsuto Tsunoda, Yoshikazu Tamori, Wataru Ogawa

    D-47 is a newly developed solid dispersion of the arginine salt of (S)-(+)-4-[1-(4-tert-butylphenyl)-2-oxo-pyrrolidin-4-yl]methoxybenzoic acid (S-2E), which inhibits sterol and fatty acid synthesis. D-47 was recently shown to lower the serum level and hepatic content of both triglyceride and cholesterol in a rabbit model of familial hypercholesterolemia. We here investigated the effects of D-47 on dyslipidemia and hepatic steatosis in comparison with those of bezafibrate in the db/db mouse model of obesity. Treatment of db/db mice with D-47 or bezafibrate for 14 days lowered the serum triglyceride concentration without affecting that of cholesterol. D-47, but not bezafibrate, almost completely eliminated lipid droplets in hepatocytes and markedly lowered the triglyceride content of the liver in these mice. The two agents induced similar changes in the hepatic expression of genes including those related to β-oxidation or fatty acid synthesis. D-47 however significantly reduced the mass of white adipose tissue and up-regulated the expression of genes related to energy expenditure, mitochondrial function, fatty acid oxidation or lipolysis in this tissue, indicating that D-47 induced the brown/beige adipocyte-like change in white adipose tissue, whereas bezafibrate had no such effects. Treatment of 3T3-L1 adipocytes with D-47 provoked the expression of genes related to mitochondrial function, fatty acid oxidation or lipolysis. Our data have thus shown that D-47 ameliorated hypertriglyceridemia and hepatic steatosis in an animal model of obesity, and they suggest that this latter effect might be mediated through the change of adipose tissue characteristics.

    2019年06月17日, The Kobe journal of medical sciences, 65 (1), E36-E43, 英語, 国内誌

    [査読有り]

  • Sleeve Gastrectomy Induced Remission of Slowly Progressive Type 1 Diabetes in a Morbidly Obese Japanese Patient

    Hironaka JY, Kitahama S, Sato H, Inoue M, Takahashi T, Tamori Y

    2019年03月, Intern Med, 58 (5), 675 - 678, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Nakajima S, Nishimoto Y, Tateya S, Iwahashi Y, Okamatsu-Ogura Y, Saito M, Ogawa W, Tamori Y

    AIMS/INTRODUCTION: Fat-specific protein 27 (FSP27) α is the major isoform of FSP27 in white adipose tissue (WAT), and is essential for large unilocular lipid droplet (LD) formation in white adipocytes. In contrast, FSP27β is abundantly expressed in brown adipose tissue (BAT), and plays an important role in small multilocular LD formation. In FSP27 KO mice in which FSP27α and β are both depleted, WAT is characterized by multilocular LD formation, and by increased mitochondrial abundance and energy expenditure, whereas BAT conversely manifests large oligolocular LDs and reduced energy expenditure. MATERIALS AND METHODS: We investigated the effects of autophagy in WAT and BAT of wild type (WT) and FSP27 knockout (KO) mice. In addition, we examined the effects of FSP27α and FSP27β to the induction of autophagy in COS cells. RESULTS: Food deprivation induced autophagy in BAT of WT mice, as well as in WAT of FSP27 KO mice, suggesting that enhanced autophagy is characteristic of adipocytes with small multilocular LDs. Pharmacological inhibition of autophagy attenuated the fasting-induced loss of LD area in adipocytes with small multilocular LDs (BAT of WT mice and WAT of FSP27 KO mice), without affecting that in adipocytes with large unilocular or oligolocular LDs (WAT of WT mice or in BAT of FSP27 KO mice). Overexpression of FSP27α inhibited autophagy induction by serum deprivation in COS cells, whereas that of FSP27β had no such effect. CONCLUSIONS: The present results thus showed that FSP27α inhibits autophagy and might thereby contribute to the energy-storage function of WAT.

    2019年03月, J Diabetes Investig, 10 (6), 1419 - 1429, 英語, 国内誌

    [査読有り]

    研究論文(学術雑誌)

  • Hiroshi Miura, Kazuhiko Sakaguchi, Yuko Okada, Natsu Otowa-Suematsu, Tomoko Yamada, Anna So, Hisako Komada, Yushi Hirota, Minoru Kishi, Akihiko Takeda, Yoichi Tominaga, Tomoaki Nakamura, Yasuo Kuroki, Tomokazu Matsuda, Keiji Iida, Michiko Kajikawa, Takeshi Ohara, Kazuki Yokota, Kenta Hara, Sanshiro Tateya, Yoshikazu Tamori, Wataru Ogawa

    INTRODUCTION: Administered basal insulin markedly influences the fasting plasma glucose (FPG) level of individuals with type 1 diabetes. Insulin degludec (IDeg) and insulin glargine U300 (IGlar U300) are now available as ultra-long-acting insulin formulations, but whether or how their glucose-stabilizing effects differ remains unclear. We will compare the effects of these basal insulins on parameters related to blood glucose control, with a focus on day-to-day glycemic variability, in individuals with type 1 diabetes treated with multiple daily injections. METHODS: A multicenter, randomized, open-label, crossover, comparative study (Kobe Best Basal Insulin Study 2) will be performed at 13 participating institutions in Japan. A total of 46 C-peptide-negative adult outpatients with type 1 diabetes will be randomly assigned 1:1 by a centralized allocation process to IGlar U300 (first period)/IDeg (second period) or IDeg (first period)/IGlar U300 (second period) groups, in which subjects will be treated with the corresponding basal insulin for consecutive 4-week periods. The basal insulin will be titrated to achieve an FPG of less than 130 mg/dL initially and then less than 110 mg/dL if feasible. In the last week of each period, plasma glucose will be determined seven times a day by self-monitoring of blood glucose (SMBG) and intraday and day-to-day glucose excursions will be determined by flash glucose monitoring (FGM). The primary end point is comparison of day-to-day glycemic variability as evaluated by the standard deviation (SD) of FPG during the last week of each treatment period. Secondary end points include the coefficient of variance of FPG, the frequency of severe hypoglycemia as evaluated by SMBG, the duration of hypoglycemia as evaluated by FGM, intraday glycemic variability calculated from both SMBG and FGM data, and the administered insulin dose. PLANNED OUTCOMES: The results of the study will be submitted for publication in a peer-reviewed journal to report differences in the effects of two ultra-long-acting basal insulins, IDeg and IGlar U300. CONCLUSION: This head-to-head comparison will be the first study to compare the effects of IDeg and IGlar U300 on day-to-day FPG variability in C-peptide-negative individuals with type 1 diabetes. TRIAL REGISTRATION: Registered in University Hospital Medical Information Network (UMIN) Clinical Trials Registry as 000029630 on 20 June 2017. FUNDING: Novo Nordisk Pharma Ltd.

    2018年12月, Diabetes therapy : research, treatment and education of diabetes and related disorders, 9 (6), 2399 - 2406, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Natsu Otowa-Suematsu, Kazuhiko Sakaguchi, Tomoaki Nakamura, Kenta Hara, Minoru Kishi, Naoko Hashimoto, Kazuki Yokota, Hiroshi Yoshino, Yasuo Kuroki, Tomoko Nishiumi, Anna Sou, Hisako Komada, Yuko Okada, Yushi Hirota, Yoshikazu Tamori, Wataru Ogawa

    INTRODUCTION: We comprehensively evaluated the effects of combination therapy with insulin glargine and the incretin-based drugs lixisenatide or vildagliptin in Japanese patients with type 2 diabetes. METHODS: In this 12-week, randomized, open-label, parallel-group, multicenter study (GLP-ONE Kobe), the incretin-based drug sitagliptin was randomly switched to lixisenatide (20 μg/day, n = 18) or vildagliptin (100 mg/day, n = 20) in patients with inadequate glycemic control despite combination therapy with insulin glargine and sitagliptin. The dose of insulin glargine was titrated after the switch to maintain fasting blood glucose at approximately 110 mg/dL. The primary end points of the study were the change in glycosylated hemoglobin (HbA1c) level between before and 12 weeks after the treatment switch, the proportion of patients achieving an HbA1c level below 7.0%, and the postprandial increase in glucose concentration as assessed by self-monitoring of blood glucose. RESULTS: The change in HbA1c level from baseline to 12 weeks did not differ significantly between the lixisenatide and vildagliptin groups (- 0.6 ± 0.7% and - 0.6 ± 1.2%, respectively, P = 0.920). Neither the proportion of patients achieving an HbA1c level below 7.0% nor the postprandial increase in glucose concentration was different between two groups. Body weight and serum low density lipoprotein (LDL) cholesterol level decreased significantly in the lixisenatide and vildagliptin groups, respectively. Both drugs were associated with mild gastrointestinal symptoms but not with severe hypoglycemia. Vildagliptin was associated with elevation of serum aspartate transaminase. Treatment satisfaction as assessed with the Diabetes Treatment Satisfaction Questionnaire did not differ significantly between the two groups. CONCLUSION: The combinations of basal insulin and either lixisenatide or vildagliptin have similar efficacies with regard to improvement of glycemic control. TRIAL REGISTRATION: This trial has been registered with UMIN (No. 000010769).

    2018年10月, Diabetes therapy : research, treatment and education of diabetes and related disorders, 9 (5), 2067 - 2079, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • 高橋 路子, 三ヶ尻 礼子, 田渕 聡子, 脇田 くみこ, 山西 美沙, 山下 弘子, 玉田 萌子, 西田 ひかる, 中谷 早希, 向山 万為子, 斎藤 紗緒理, 諫山 叶実, 河村 弘美, 山本 育子, 多和田 尚子, 岡田 裕子, 廣田 勇士, 北浜 誠一, 田守 義和, 小川 渉

    (一社)日本肥満学会, 2018年09月, 肥満研究, 24 (Suppl.), 181 - 181, 日本語

  • 腎盂腎炎類似の症状を呈する脊柱起立筋膿瘍を発症した2型糖尿病の1例

    佐藤洋幸, 岩橋泰幸, 瀬尾あかね, 井上真希, 高橋哲也, 田守義和

    2018年07月, 愛仁会医学研究誌, 49, 17 - 19, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • Nishimoto Y, Nakajima S, Tateya S, Saito M, Ogawa W, Tamori Y

    Adipose tissue stores neutral lipids and is a major metabolic organ involved in regulating whole-body energy homeostasis. Triacylglycerol is stored as unilocular large lipid droplets (LDs) in white adipocytes and as multilocular small LDs in brown adipocytes. Proteins of the cell death-inducing DNA fragmentation factor A-like effector (Cide) family include CideA, CideB, and fat-specific protein of 27 (FSP27). Of these, FSP27 has been shown to play a crucial role in the formation of unilocular large LDs in white adipocytes. However, the mechanisms by which brown adipocytes store small and multilocular LDs remain unclear. An FSP27 isoform, FSP27 beta, was recently identified. We herein report that CideA and FSP27 beta are mainly expressed in brown adipose tissue and that FSP27 beta overexpression inhibits CideA-induced LD enlargements in a dose-dependent manner in COS cells. Furthermore, RNAi-mediated FSP27 beta depletion resulted in enlarged LDs in HB2 adipocytes, which possess the characteristics of brown adipocytes. Brown adipocytes in FSP27-knock-out mice that express CideA, but not FSP27 beta, had larger and fewer LDs. Moreover, we confirmed that FSP27 beta and CideA form a complex in brown adipose tissue. Our results suggest that FSP27 beta negatively regulates CideA-promoted enlargement of LD size in brown adipocytes. FSP27 beta appears to be responsible for the formation of small and multilocular LDs in brown adipose tissue, a morphology facilitating free fatty acid transport to mitochondria adjacent to LDs for oxidation in brown adipocytes.

    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017年06月, J Biol Chem, 292 (26), 10824 - 10834, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Evaluation of metabolic parameters and body composition in Japanese patients with type 2 diabetes mellitus who were administered tofogliflozin for 48 weeks

    Iwahashi Y, Hirose S, Nakajima S, Seo A, Takahashi T, Tamori Y

    2016年11月, Diabetol Int, 8 (2), 205 - 211, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yoshinaga Kawano, Jun Nakae, Nobuyuki Watanabe, Tetsuhiro Kikuchi, Sanshiro Tateya, Yoshikazu Tamori, Mari Kaneko, Takaya Abe, Masafumi Onodera, Hiroshi Itoh

    High-fat diet (HFD) induces low-grade chronic inflammation and insulin resistance. However, little is known about the mechanism underlying HFD-induced chronic inflammation in peripheral insulin- responsive tissues. Here, we show that colonic pro-inflammatory macrophages regulate insulin sensitivity under HFD conditions. To investigate the pathophysiological role of colonic macrophages, we generated macrophage-specific chemokine (C-C Motif) receptor 2 (Ccr2) knockout (M-Ccr2KO) and intestinal epithelial cell-specific tamoxifen-inducible Ccl2 knockout (Vil-Ccl2KO) mice. Both strains exhibited similar body weight to control under HFD. However, they exhibited decreased infiltration of colonic pro-inflammatory macrophages, decreased intestinal permeability, and inactivation of the colonic inflammasome. Interestingly, they showed significantly improved glucose tolerance and insulin sensitivity with decreased chronic inflammation of adipose tissue. Therefore, inhibition of pro-inflammatory macrophage infiltration prevents HFD-induced insulin resistance and could be a novel therapeutic approach for type 2 diabetes.

    CELL PRESS, 2016年08月, CELL METABOLISM, 24 (2), 295 - 310, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yoshikazu Tamori, Sanshiro Tateya, Takeshi Ijuin, Yuki Nishimoto, Shinsuke Nakajima, Wataru Ogawa

    FSP27 has an important role in large lipid droplet (LD) formation because it exchanges lipids at the contact site between LDs. In the present study, we clarify that the amino-terminal domain of FSP27 (amino acids 1-130) is dispensable for LD enlargement, although it accelerates LD growth. LD expansion depends on the carboxy-terminal domain of FSP27 (amino acids 131-239). Especially, the negative charge of the acidic residues (D215, E218, E219 and E220) in the polar carboxy-terminal region (amino acids 202-239) is essential for the enlargement of LD. We propose that the carboxy-terminal domain of FSP27 has a crucial role in LD expansion, whereas the amino-terminal domain only has a supportive role.

    WILEY, 2016年03月, FEBS LETTERS, 590 (6), 750 - 759, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yoshikazu Tamori, Sanshiro Tateya, Takeshi Ijuin, Yuki Nishimoto, Shinsuke Nakajima, Wataru Ogawa

    FSP27 has an important role in large lipid droplet (LD) formation because it exchanges lipids at the contact site between LDs. In the present study, we clarify that the amino-terminal domain of FSP27 (amino acids 1-130) is dispensable for LD enlargement, although it accelerates LD growth. LD expansion depends on the carboxy-terminal domain of FSP27 (amino acids 131-239). Especially, the negative charge of the acidic residues (D215, E218, E219 and E220) in the polar carboxy-terminal region (amino acids 202-239) is essential for the enlargement of LD. We propose that the carboxy-terminal domain of FSP27 has a crucial role in LD expansion, whereas the amino-terminal domain only has a supportive role.

    2016年03月, FEBS letters, 590 (6), 750 - 9, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Sachie Hirose, Shinsuke Nakajima, Yasuyuki Iwahashi, Akane Seo, Tetsuya Takahashi, Yoshikazu Tamori

    Objective The adverse effects of selective sodium-glucose co-transporter 2 (SGLT2) inhibitors generally appear within about two or three months after treatment initiation in Japan. Therefore, we investigated the impact of tofogliflozin, a class of SGLT2 inhibitors, on glycemic control and body composition during this period in Japanese patients with type 2 diabetes mellitus. Methods This single-arm open-label study enrolled 20 patients. Patients received tofogliflozin 20 mg once daily for 8 weeks. At week 8, changes from baseline in body weight, serum metabolic markers, and body composition were evaluated. Results A total of 17 patients completed the 8-week administration of tofogliflodin. No serious adverse events were noted. Hemoglobin A1c (HbA1c) decreased significantly, from 7.8% to 7.3% with 8-week administration of tofogliflozin. Both the body weight and body mass index (BMI) also decreased. In addition, a decreased renal function of the boundary zone and hemoconcentration were detected. As for body composition, the free fat mass, total body water, extracellular water and intracellular water were all decreased significantly. Interestingly, the amount of fat mass did not change. The degree of improvement in HbA1c was correlated with the baseline fat mass and BMI. Conclusion An eight-week administration of tofogliflozin improved glycemic control and reduced the body weight and free fat mass in type 2 diabetic patients without affecting the fat mass. In this period, the hematocrit level and renal function should be monitored to guard against hemoconcentration and renal impairment, respectively.

    JAPAN SOC INTERNAL MEDICINE, 2016年, INTERNAL MEDICINE, 55 (22), 3239 - 3245, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Sachie Hirose, Yasuyuki Iwahashi, Akane Seo, Michitaka Sumiyoshi, Tetsuya Takahashi, Yoshikazu Tamori

    Reactive hypoglycemia induced by late dumping syndrome is often observed after gastrectomy. However, no effective therapy has yet been fully established. We herein describe a case in which concurrent therapy with a low-carbohydrate diet using low-glycemic-index food and an alpha-glucosidase inhibitor, miglitol, very effectively ameliorated the postprandial fluctuations in the blood glucose and plasma insulin levels in a patient with reactive hypoglycemia due to late dumping syndrome following total gastrectomy. The administration of miglitol under a low-carbohydrate diet using low-glycemic-index food may therefore be an ideal treatment for reactive hypoglycemia due to late dumping syndrome.

    JAPAN SOC INTERNAL MEDICINE, 2016年, INTERNAL MEDICINE, 55 (9), 1137 - 1142, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Insulin resistance and white adipose tissue inflammation are uncoupled in energetically challenged Fsp27-deficient mice

    ZhouL, ParkSY, XuL, XiaX, YeJ, SuL, JeongKH, HurJH, OhH, TamoriY, ZingarettiCM, CintiS, ArgenteJ, YuM, WuL, JuS, GuanF, YangH, ChoiCS, SavageDB, LiP

    2015年01月, Nat Commun, 6, 5949, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Circulating progranulin level is associated with visceral fat and elevated liver enzymes: Significance of serum progranulin as a useful marker for liver dysfunction

    Yuko Tanaka, Tetsuya Takahashi, Yoshikazu Tamori

    Progranulin (PRGN) was recently identified as one of the adipokines involved in the development of insulin resistance. Thus, the aim of this study was to explore the importance of PRGN as a novel marker for metabolic diseases in Japanese. A total of 138 subjects were recruited by the Aijinkai Total Health Care Center. Physical examination, blood sample examination and total body CT scan were performed for all participants. Serum PRGN levels were examined in subjects with or without metabolic syndrome and with or without liver enzyme elevation. Association study of serum PRGN levels and regression analysis of the relationship of elevated liver enzymes to representative metabolic parameters were performed. The metabolic syndrome group exhibited older age, and higher BMI, blood pressure, fasting glucose, HbA1c, IRI, HOMA-R, TG, FFA, CRP, AST, ALT, LDH, and ALP, and larger visceral fat area, subcutaneous fat area and visceral fat area/subcutaneous fat area. Serum PRGN concentrations were significantly higher in the metabolic syndrome group than in the non-metabolic syndrome group. Bivariate correlation analysis revealed that serum PRGN concentrations correlated positively and significantly with AST, ALT, LDH, gamma GTP, ALP, waist circumference and visceral fat area. The group with elevated liver enzymes exhibited higher BMI, blood pressure, IRI, HOMA-R, and PRGN level and larger waist circumference and visceral fat area than the group without them. In logistic regression analysis, visceral fat area and PRGN were significantly predictive of elevated liver enzymes. These results suggest that serum PRGN level as well as visceral fat are associated closely with liver dysfunction.

    JAPAN ENDOCRINE SOC, 2014年12月, ENDOCRINE JOURNAL, 61 (12), 1191 - 1196, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 確定診断を契機に血糖コントロールを良好にし得た異常ヘモグロビン症の1例

    佐々木由佳, 高橋哲也, 三浦洋, 田中裕子, 廣瀬幸恵, 大野恭太, 喜多哲也, 田守義和

    2014年12月, Diabetes Journal: 糖尿病と代謝, 42 (4号), 163 - 167, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • 妊娠糖尿病患者の背景と食生活を中心としたライフスタイルの特徴

    中村愛美, 濱本, 山田成子, 矢野真友美, 田中裕子, 佐々木由佳, 中東, 岡田十三, 本山覚, 高橋哲也, 田守義和

    当院妊娠糖尿病患者(GDM)の背景及びライフスタイルを調査した。妊婦健診の患者1032名に随時血糖によるGDMスクリーニング検査を行い、随時血糖100mg/dl以上のスクリーニング陽性者に食生活に関する問診票を配布し、75g経口ブドウ糖負荷試験(75gOGTT)と栄養相談を実施した。スクリーニング陽性者は167名で、この内GDMは21名(妊婦健診受診者の2.0%)、非GDMは146名であった。糖尿病の家族歴はGDM群が非GDM群に比べ有意に多かった。妊娠前BMIはGDM群が非GDM群に比べ高い傾向にあった(P=0.06)。随時血糖値には有意差を認めなかった。HbA1cはGDM群が有意に高かった。また、GDM21名の診断基準陽性の点数内訳では、非妊娠時BMI25以上の妊婦の点数が有意に高かった。生活背景に関しては、間食や外食の頻度には差を認めなかったものの、GDM群には妊娠前に油ものを好む者が有意に多かった。またGDM群は夕食時間が遅い(20時以降)傾向があり(P=0.09)、睡眠時間が短い者(6時間以下)が有意に多かった。以上、GDMの背景として、糖尿病家族歴や非妊娠時BMIが高く、食生活では油ものを好み、夕食時間が遅く、睡眠時間も短い等のライフスタイルの特徴が明らかになった。(著者抄録)

    (一社)日本病態栄養学会, 2014年09月, 日本病態栄養学会誌, 17 (3号), 357 - 365, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • 糖尿病発症におけるインクレチン効果の疫学的研究(第3報) 妊娠糖尿病のスクリーニングからのアプローチ

    田守義和, 田中裕子, 高橋哲也, 岡田十三

    2014年08月, 神緑会学術誌, 30, 7 - 9, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • 糖尿病発症におけるインクレチン効果の疫学的研究(第2報) 妊娠糖尿病のスクリーニングからのアプローチ

    田守義和, 田中裕子, 高橋哲也, 岡田十三

    2013年08月, 神緑会学術誌, 29, 7 - 10, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • 化学療法患者の食事の個別対応における当院の取り組み

    濱本愛美, 山田成子, 矢野真友美, 多田明弘, 田守義和, 高橋哲也

    当院では化学療法中のがん患者に対し、「いつ誰が食事の個別介入をするか」の取り決めがなく、介入が必要な患者に対して的確に対応できていないのではないかと考えられた。そこで今回、現状を調査し、明らかになった課題への取り組みを行った。現状調査の結果、「化学療法中に食欲がない」と答えた患者が71%、「希望すれば個別の食事対応ができることを知らない」と答えた患者が47%で、食事未介入率は30%であった。取り組みとして、管理栄養士が介入できる体制づくりを目指し、個別介入対象者の把握は入院時栄養管理計画書と電子カルテの予定入院枠を併用することで早期介入を達成した。また、個別対応可能なメニューや食品を新たに設定し、さらに介入者の差異を解消するため、個別の症状・嗜好に配慮してアセスメントできるよう「食事聞き取りシート」を作成した。

    (社医)愛仁会本部, 2013年03月, 愛仁会医学研究誌, 44, 224 - 226, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • バセドウ病と進行食道癌による低T3症候群を合併した1例

    大野恭太, 高橋哲也, 田守義和, 中東由佳, 田中裕子, 三浦洋, 喜多哲也

    2013年03月, 愛仁会医学研究誌, 44, 105 - 107, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • 妊娠初期に急性膵炎が先行して発症した劇症1型糖尿病の1例

    中島進介, 高橋哲也, 田中裕子, 西本祐希, 中東由佳, 大野恭太, 喜多哲也, 田守義和

    2012年12月, 糖尿病, 55 (12号), 987 - 992, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • 糖尿病発症におけるインクレチン効果の疫学的研究(第一報) 妊娠糖尿病のスクリーニングからのアプローチ

    田守義和, 田中裕子, 高橋哲也, 岡田十三

    2012年08月, 神緑会学術誌, 28, 5 - 7, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • Toshiya Matsubara, Ayako Mita, Kohtaro Minami, Tetsuya Hosooka, Sohei Kitazawa, Kenichi Takahashi, Yoshikazu Tamori, Norihide Yokoi, Makoto Watanabe, Ei-Ichi Matsuo, Osamu Nishimura, Susumu Seino

    Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn(-/-)) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity.

    2012年01月04日, Cell metabolism, 15 (1), 38 - 50, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • 心嚢液貯留と著明な肝障害を認めた甲状腺機能低下症の1例

    出口令子, 高橋哲也, 西本祐希, 中島進介, 大野恭太, 喜多哲也, 尾崎正憲, 二宮幸三, 松森佳子, 田守義和, 筒泉正春

    2011年05月, 愛仁会医学研究誌, 42, 53 - 57, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • 過食により糖尿病性ケトーシスを発症した成人期ダウン症候群の1例

    西本祐希, 高橋哲也, 出口令子, 中島進介, 大野恭太, 喜多哲也, 筒泉正春, 中岡大樹, 田守義和

    2011年05月, 愛仁会医学研究誌, 42, 58 - 61, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • 下肢筋力低下で発症し、剖検にて胸髄の梗塞が認められた血管内リンパ腫(IVL)の1例

    柏木孝夫, 大野恭太, 喜多哲也, 高橋哲也, 田守義和, 船津英司, 當銘成友, 那賀川峻, 伊藤成規, 名方保夫

    2011年05月, 愛仁会医学研究誌, 42, 62 - 64, 日本語

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • RanjitS, BoutetE, GandhiP, ProtM, TamoriY, ChawlaA, GreenbergAS, PuriV, CzechMP

    The lipid droplet-associated fat specific protein 27 (FSP27) suppresses lipolysis and thereby enhances triglyceride accumulation in adipocytes. We and others have recently found FSP27 to be a remarkably short-lived protein (half-life, 15 min) due to its rapid ubiquitination and proteasomal degradation. Thus, we tested the hypothesis that lipolytic agents such as tumor necrosis factor-alpha (TNF-alpha) and isoproterenol modulate FSP27 levels to regulate FFA release. Consistent with this concept, we showed that the lipolytic actions of TNF-alpha, interleukin-1 beta (IL-1 beta), and IFN-gamma are accompanied by marked decreases in FSP27 expression and lipid droplet size in mouse adipocytes. Similar depletion of FSP27 using short interfering RNA (siRNA) mimicked the lipolysis-enhancing effect of TNF-alpha, while maintaining stable FSP27 levels using expression of hemagglutinin epitope-tagged FSP27 blocked TNF-alpha-mediated lipolysis. In contrast, we show the robust lipolytic action of isoproterenol is paradoxically associated with increases in FSP27 levels and a delayed degradation rate corresponding to decreased ubiquitination. This catecholamine-mediated increase in FSP27 abundance, probably a feedback mechanism for restraining excessive lipolysis by catecholamines, is mimicked by forskolin or 8-bromo-cAMP treatment and is prevented by the protein kinase A (PKA) inhibitor KT5720 or by PKA depletion using siRNA. Taken together, these data identify the regulation of FSP27 as an important intermediate in the mechanism of lipolysis in adipocytes in response to TNF-alpha and isoproterenol.-Ranjit, S., E. Boutet, P. Gandhi, M. Prot, Y. Tamori, A. Chawla, A. S. Greenberg, V. Puri, and M. P. Czech. Regulation of fat specific protein 27 by isoproterenol and TNF-alpha to control lipolysis in murine adipocytes. J. Lipid Res. 2011. 52: 221-236.

    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2011年02月, J Lipid Res, 52 (2), 221 - 236, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 高度な肥満を伴い著明な高尿酸血症、急性腎不全、肺血栓塞栓症、急性胃粘膜病変を相次いで併発した清涼飲料水ケトアシドーシスの1例

    高橋哲也, 中島進介, 大野恭太, 尾崎正憲, 西本祐希, 喜多哲也, 筒泉正春, 田守義和

    2010年09月, Diabetes Journal: 糖尿病と代謝, 38 (3号), 109 - 114, 日本語

    [査読有り]

    研究論文(学術雑誌)

  • Shuji Ueda, Sohei Kitazawa, Kota Ishida, Yuki Nishikawa, Megumi Matsui, Hikaru Matsumoto, Takuji Aoki, Shinsuke Nozaki, Tomoya Takeda, Yoshikazu Tamori, Atsu Aiba, C. Ronald Kahn, Tohru Kataoka, Takaya Satoh

    The Rho family GTPase Rac1 has been implicated in the regulation of glucose uptake in myoblast cell lines. However, no evidence for the role of Rac1 has been provided by a mouse model. The purpose of this study is to test the involvement of Rac1 in insulin action in mouse skeletal muscle. Intravenous administration of insulin indeed elicited Rac1 activation in gastrocnemius muscle, suggesting the involvement of Rac1 in this signaling pathway. We then examined whether insulin-stimulated translocation of the facilitative glucose transporter GLUT4 from its storage sites to the skeletal muscle sarcolemma depends on Rac1. We show that ectopic expression of constitutively activated Rac1, as well as intravenous administration of insulin, caused translocation of GLUT4 to the gastrocnemius muscle sarcolemma, as revealed by immunofluorescent staining of a transiently expressed exofacial epitope-tagged GLUT4 reporter. Of particular note, insulin-dependent, but not constitutively activated Rac1-induced, GLUT4 translocation was markedly suppressed in skeletal muscle-specific rac1-knockout mice compared to control mice. Immunogold electron microscopic analysis of endogenous GLUT4 gave similar results. Collectively, we propose a critical role of Rac1 in insulin-dependent GLUT4 translocation to the skeletal muscle sarcolemma, which has heretofore been predicted solely by cell culture studies. © FASEB.

    2010年07月, FASEB Journal, 24 (7), 2254 - 2261, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Sanshiro Tateya, Yoshikazu Tamori, Takayuki Kawaguchi, Hajime Kanda, Masato Kasuga

    Chronic inflammation in adipose tissue is thought to be important for the development of insulin resistance in obesity. Furthermore, the level of monocyte chemoattractant protein-1 (MCP-1) is increased not only in adipose tissue but also in the circulation in association with obesity. However, it has remained unclear to what extent the increased circulating level of MCP-1 contributes to insulin resistance. We have now examined the relevance of circulating MCP-1 to the development of insulin resistance in mice. The plasma concentration of MCP-1 was increased chronically or acutely in mice to the level observed in obese animals by chronic subcutaneous infusion of recombinant MCP-1 with an osmotic pump or by acute intravenous infusion of MCP-1 with an infusion pump, respectively. Whole-body metabolic parameters as well as inflammatory changes in adipose tissue were examined. A chronic increase in the circulating level of MCP-1 induced insulin resistance, macrophage infiltration into adipose tissue, and an increase in hepatic triacylglycerol content. An acute increase in the circulating MCP-1 concentration also induced insulin resistance but not macrophage infiltration into adipose tissue. In addition, inhibition of signaling by MCP-1 and its receptor CCR2 by administration of a novel CCR2 antagonist ameliorated insulin resistance in mice fed a high-fat diet without affecting macrophage infiltration into adipose tissue. These data indicate that an increase in the concentration of MCP-1 in the circulation is sufficient to induce systemic insulin resistance irrespective of adipose tissue inflammation. (Endocrinology 151: 971-979, 2010)

    ENDOCRINE SOC, 2010年03月, ENDOCRINOLOGY, 151 (3), 971 - 979, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Takayuki Kawaguchi, Yoshikazu Tamori, Hajime Kanda, Mari Yoshikawa, Sanshiro Tateya, Naonobu Nishino, Masato Kasuga

    SNARE proteins (VAMP2, syntaxin4, and SNAP23) have been thought to play a key role in GLUT4 trafficking by mediating the tethering, clocking and subsequent fusion of GLUT4-containing vesicles with the plasma membrane. The precise functions of these proteins have remained elusive, however. We have now shown that depletion of the vesicle SNARE (v-SNARE) VAMP2 by RNA interference in 3T3-L1 adipocytes inhibited the fusion of GLUT4 vesicles with the plasma membrane but did not affect tethering of the vesicles to the membrane. In contrast, depletion of the target SNAREs (t-SNAREs) syntaxin4 or SNAP23 resulted in impairment of GLUT4 vesicle tethering to the plasma membrane. Our results indicate that the t-SNAREs syntaxin4 and SNAP23 are indispensable for the tethering of GLUT4 vesicles to the plasma membrane, whereas the v-SNARE VAMP2 is not required for this step but is essential for the subsequent fusion event. (C) 2009 Elsevier Inc. All rights reserved.

    ACADEMIC PRESS INC ELSEVIER SCIENCE, 2010年01月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 391 (3), 1336 - 1341, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Cervical epidural abscess presenting with Brown-Sequard syndrome in a patient with type 2 diabetes

    TamoriY, TakahashiT, SuwaH, OhnoK, NishimotoY, NakajimaS, AsadaM, KitaT, TsutsumiM

    2010年, Intern Med, 49 (14), 1391 - 3, 英語

    [査読有り]

    研究論文(学術雑誌)

  • エネルギー代謝と肥満症 脂肪細胞における脂肪滴蓄積形態とエネルギー代謝

    田守義和

    2009年09月, 肥満研究, 15巻, Suppl., pp. 133-133, 日本語

    研究論文(国際会議プロシーディングス)

  • 肥満脂肪細胞の病態 脂肪滴蛋白FSP27が制御する脂肪滴形成と高効率の中性脂肪蓄積機構の解明

    田守義和

    2008年09月, 肥満研究, 14巻, Suppl., pp. 91-91, 日本語

    研究論文(国際会議プロシーディングス)

  • Takeshi Ijuin, Y. Eugene Yu, Kiyohito Mizutani, Annie Pao, Sanshiro Tateya, Yoshikazu Tamori, Allan Bradley, Tadaomi Takenawa

    Insulin controls glucose homeostasis and lipid metabolism, and insulin impairment plays a critical role in the pathogenesis of diabetes mellitus. Human skeletal muscle and kidney enriched inositol polyphosphate phosphatase (SKIP) is a member of the phosphatidylinositol 3,4,5-trisphosphate phosphatase family (T. Ijuin et al. J. Biol. Chem. 275: 10870-10875, 2000; T. Ijuin and T. Takenawa, Mol. Cell. Biol. 23: 1209-1220, 2003). Previous studies showed that SKIP negatively regulates insulin-induced phosphatidylinositol 3-kinase signaling (Ijuin and Takenawa, Mol. Cell. Biol. 23: 1209-1220, 2003). We now have generated mice with a targeted mutation of the mouse ortholog of the human SKIP gene, Pps. Adult heterozygous Pps mutant mice show increased insulin sensitivity and reduced diet-induced obesity with increased Akt/protein kinase B (PKB) phosphorylation in skeletal muscle but not in adipose tissue. The insulin-induced uptake of 2-deoxyglucose into the isolated soleus muscle was significantly enhanced in Pps mutant mice. A hyperinsulinemic-euglycemic clamp study also revealed a significant increase in the rate of systemic glucose disposal in Pps mutant mice without any abnormalities in hepatic glucose production. Furthermore, in vitro knockdown studies in L6 myoblast cells revealed that reduction of SKIP expression level increased insulin-stimulated Akt/PKB phosphorylation and 2-deoxyglucose uptake. These results imply that SKIP regulates insulin signaling in skeletal muscle. Thus, SKIP may be a promising pharmacologic target for the treatment of insulin resistance and diabetes.

    AMER SOC MICROBIOLOGY, 2008年09月, MOLECULAR AND CELLULAR BIOLOGY, 28 (17), 5184 - 5195, 英語

    研究論文(学術雑誌)

  • FSP27 contributes to efficient energy storage in murine white adipocytes by promoting the formation of unilocular lipid droplets

    Nishino N, Tamori Y, Kitazawa R, Kitazawa S, Nakao H, Aiba A

    2008年08月, The Journal of clinical investigation, Vol. 118, No. 8, pp. 2808-21, 英語

    [査読有り]

    研究論文(学術雑誌)

  • target-SNARE(syntaxin4 and SNAP23)は脂肪細胞においてexocyst複合体と協調してGLUT4小胞を細胞膜に繋留するのに重要な機能を担う

    田守義和

    2008年07月, 日本臨床分子医学会学術総会プログラム・抄録集45回, 巻, , pp. 71-71, 日本語

    研究論文(国際会議プロシーディングス)

  • 脂肪滴蛋白FSP27は単房性の脂肪滴形成を介して白色脂肪に効率よく中性脂肪を蓄積する

    田守義和

    2008年04月, 糖尿病, 51巻, Suppl.1, pp. S-306, 日本語

    研究論文(国際会議プロシーディングス)

  • 2型糖尿病患者の食事・運動療法の実施状況における背景要因の検討

    田守義和, 野口哲也

    2008年04月, 糖尿病, 51巻, Suppl.1, pp. S-170, 日本語

    研究論文(国際会議プロシーディングス)

  • 2型糖尿病患者の初回受診前から1年間の自己管理行動実施における経験<食事・運動療法実施良好群と不良群との比較>

    田守義和, 野口哲也

    2008年04月, 糖尿病, 51巻, Suppl.1, pp. S-380, 日本語

    研究論文(国際会議プロシーディングス)

  • 2型糖尿病患者の初回受診前から1年間の血糖およびBMIの推移<食事・運動療法実施良好群と不良群との比較

    田守義和, 野口哲也

    2008年04月, 糖尿病, 51巻, Suppl.1, pp. S-281, 日本語

    研究論文(国際会議プロシーディングス)

  • Association of serum MCP-1 concentration and MCP-1 polymorphism with insulin resistance in Japanese individuals with obese type 2 diabetes

    Hirota Y, Tamori Y

    2008年02月, The Kobe journal of medical sciences, Vol. 53, No. 6, pp. 345-54, 英語

    研究論文(学術雑誌)

  • Insulin-stimulated fusion of GLUT4 vesicles to plasma membrane is dependent on wortmannin-sensitive insulin signaling pathway in 3T3-L1 adipocytes

    Takayuki Kawaguchi, Yoshikazu Tamori, Mari Yoshikawa, Hajime Kanda, Masato Kasuga

    It is established that wortmannin which completely inhibits class IA PI 3-kinase activation abrogated the insulin-dependent translocation of GLUT4 to the plasma membrane in adipocytes and skeletal muscle. However, it was not clear which steps wortmannin inhibited during the whole translocation process of GLUT4. We have now dissected the each steps of the GLUT4 trafficking in 3T3-L1 adipocytes using exogenously-expressed GLUT4 reporter in combination with plasma membrane lawn assay. We showed that 100 nM wortmannin inhibited the fusion of GLUT4 vesicles to the plasma membrane without affecting the movement and the subsequent tethering/docking event of GLUT4 vesicles to the membrane in 3T3-L1 adipocytes. These results suggest that wortmannin-sensitive insulin signaling pathway plays a crucial role in the fusion step of GLUT4 vesicles to the plasma membrane in 3T3-L1 adipocytes.

    2008年, Kobe Journal of Medical Sciences, 54 (4), E209 - E216, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 多留ちえみ, 中渡瀬友里, 傳秋光, 田守義和, 野口哲也, 木戸良明, 大原毅, 小川渉, 宮脇郁子

    【目的】2型糖尿病患者の臨床背景に応じた具体的な療養行動支援を行うために,男女別に臨床背景(年齢,HbA1c, BMI, 腹囲)の違いによる,食事自己管理行動の実施状況と食事摂取量,およびその関連を明らかにすることを目的とした.【方法】男性99名,女性77名を対象に,食事自己管理行動(著者らの開発した調査票)と,食事摂取量(半定量食物頻度調査)を調査した.対象者は年齢60歳,HbA1c 7.0%, BMI 25, 腹囲(男性85 cm, 女性90 cm)を境界値として2群に分けた.解析にはt検定およびピアソンの相関係数を用いた.【結果】男性では,60歳未満群が,「食の満足感を高める」,「調味量のカロリーを減らす」工夫の実施率が低く,またBMI 25以上群と腹囲85 cm以上群が,「摂取量を決めて食べる」「食の満足感を高める」「バランスよく美味しく食べる」工夫の実施率が低く,摂取量の増加に関連していた.女性ではHbA1c 7.0%未満群が,「塩分制限の工夫」の実施率が高く,食事摂取量の減少に強い相関が見られた.また,60歳未満群,BMI 25以上群,腹囲90 cm以上群が,「他の価値観を優先して食べる」という一時的逸脱行動の実施率が高く,摂取量の増加に関連していた.【考察】今回明らかになった臨床背景別の特徴は,2型糖尿病患者への自己管理行動支援に活用できる.

    一般社団法人 日本糖尿病学会, 2008年, 糖尿病, 51 (2), 125 - 138, 日本語

    [査読有り]

  • 血糖コントロールの緩解増悪を繰り返すいわゆる皮下インスリン分解症候群の一例

    田守 義和

    2007年04月, 糖尿病, 50巻, Suppl.1, pp. S-123, 日本語

    研究論文(国際会議プロシーディングス)

  • 血中MCP-1の増加は脂肪組織へのマクロファージ浸潤を介する経路と介さない経路で全身のインスリン抵抗性を誘導する

    田守 義和

    2007年04月, 糖尿病, 50巻, Suppl.1, pp. S-166, 日本語

    研究論文(国際会議プロシーディングス)

  • Insulin efficiently stores triglycerides in adipocytes by inhibiting lipolysis and repressing PGC-1α induction

    Naonobu Nishino, Yoshikazu Tamori, Masato Kasuga

    White adipose tissue (WAT) is important as an energy reservoir in mammals, but the precise mechanism by which energy storage in WAT is controlled remains unclear. It is well known that representative anabolic hormone insulin efficiently stores triglyceride in adipocytes. We showed that insulin inhibited β-agonist-induced lipolysis at least in part by inhibiting phosphorylation of perilipin and hormone-sensitive lipase (HSL) in 3T3-L1 adipocytes. Furthermore, insulin inhibited β-agonist-induced increase of PGC-1α expression, which is important for mitochondrial biogenesis and energy expenditure. These results suggest the possibility that insulin efficiently stores triglyceride in adipocytes by decreasing lipolysis and repressing energy expenditure.

    2007年, Kobe Journal of Medical Sciences, 53 (3), 99 - 106, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Insulin Efficiently Stores Triglycerides in Adipocytes by Inhibiting Lipolysis and Repressing PGC-1alpha Induction

    Tamori Y

    2007年, The Kobe Journal Of Medical Sciences, Vol. 53, No. 3, pp. 99-106, 英語

    研究論文(学術雑誌)

  • 脂肪細胞研究の最前線 メタボリックシンドロームにおけるMCP-1の役割

    田守義和

    2006年09月, 肥満研究, 12巻, Suppl., pp. 134-134, 日本語

    研究論文(国際会議プロシーディングス)

  • 脂肪細胞のGLUT4小胞はExocyst complex(Sec6)を介し細胞膜に結合しv-SNARE(VAMP2)を介し融合する

    田守義和

    2006年09月, 肥満研究, 12巻, Suppl., pp. 175-175, 日本語

    研究論文(国際会議プロシーディングス)

  • メタボリックシンドロームの病態のすべて MCP-1のメタボリックシンドローム発症における病態生理学的意義

    田守義和

    2006年09月, 肥満研究, 12巻, Suppl., pp. 113-113, 日本語

    研究論文(国際会議プロシーディングス)

  • MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

    Hajime Kanda, Yoshikazu Tamori, Riko Kitazawa, Sohei Kitazawa, Masato Kasuga

    2006年06月, The Journal Of Clinical Investigation, Vol. 116, No. 6, pp. 1494-1505, 英語

    研究論文(学術雑誌)

  • 新たなアディポカインネットワーク インシュリン抵抗性に寄与するMCP1のメカニズム(Adipokine Network: a New Era: Mechanisms by which MCP-1 Contributes to Insulin Resistance)

    田守義和

    2006年04月, 糖尿病, 49巻, Suppl.1, pp. S26-S26, 日本語

    研究論文(国際会議プロシーディングス)

  • 脂肪細胞のGLUT4小胞はExocyst Complex(Sec6)を介して細胞膜に繋留しv-SNARE(VAMP2)を介して融合する

    田守義和

    2006年04月, 糖尿病, 49巻, Suppl.1, pp. S266-S266, 日本語

    研究論文(国際会議プロシーディングス)

  • メタボリック症候群 脂肪組織で発現増加するMCP-1のインスリン抵抗性に及ぼす病態的意義

    田守義和, 神田一, 楯谷三四郎, 春日雅人

    2005年07月, 日本臨床分子医学会42回学術総会プログラム・抄録集, pp.60-60, 日本語

    研究論文(国際会議プロシーディングス)

  • 肥満マウスの脂肪組織および血中で増加したMCP-1は個体レベルで肝臓のインスリン抵抗性に関与する

    田守義和

    2005年04月, 糖尿病, 48巻, Suppl.2, pp. S140-S140, 日本語

    研究論文(国際会議プロシーディングス)

  • 肥満マウスで血中MCP-1の増加は肝臓でのインスリン抵抗性に関与する

    神田一, 田守義和, 楯谷三四郎, 小谷光, 春日雅人

    2005年04月, 日本内分泌学会雑誌, 81巻, 1号, pp.84-84, 日本語

    研究論文(国際会議プロシーディングス)

  • MCP-1遺伝子上流A-2518G多型と2型糖尿病およびインスリン抵抗性との関連について

    田守義和, 鴻山訓一, 廣田勇士, 寺西卓也, 錢林雅子, 古川健亮, 大原毅, 春日雅人

    2005年02月, 日本内科学会雑誌, 94巻, Suppl., pp. 238-238, 日本語

    研究論文(国際会議プロシーディングス)

  • Adipocytes from Munc18c-null mice show increased sensitivity to insulin-stimulated GLUT4 externalization

    Kanda Hajime, Tamori Yoshikazu, Shinoda Hiroaki, Yoshikawa Mari, Sakaue Motoyoshi, Udagawa Jun, Otani Hiroki, Tashiro Fumi, Miyazaki Jun-Ichi, Kasuga Masato

    2005年, The Journal Of Clinical Investigation, Vol. 115, No. 2, pp. 291-301, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Role of peroxisome proliferator-activated receptor-gamma in maintenance of the characteristics of mature 3T3-L1 adipocytes

    Y Tamori, J Masugi, N Nishino, M Kasuga

    Peroxisome proliferator-activated receptor (PPAR)-gamma plays an important role in adipogenesis. However, the functions of PPAR-gamma in differentiated adipocytes have remained unclear. The role of PPAR-gamma in mature 3T3-L1 adipocytes was therefore investigated by overexpression of a dominant negative mutant of this protein (PPAR-gamma-DeltaC) that lacks the 16 COOH-terminal amino acids and that has been shown to prevent the thiazolidinedione-induced differentiation of 3T3-L1 cells into adipocytes. Overexpression of PPAR-gamma-DeltaC in mature 3T3-L1 adipocytes by adenovirus gene transfer resulted in a decrease in both cell size and intracellular triglyceride content, an increase in the extent of lipolysis, and a reduction in the rate of free fatty acid uptake. Furthermore, overexpression of this mutant reduced the abundance of mRNAs for several key enzymes that contribute to triglyceride and free fatty acid metabolism as well as the amounts of GLUT4, insulin receptor, insulin receptor substrate (IRS), and C/EBPalpha mRNAs. It also reduced both the concentration of IRS2 and the insulin-stimulated glucose uptake. These results suggest that PPAR-gamma plays an important role in mature 3T3-L1 adipocytes at least in part by maintaining the expression of genes that confer the characteristics of mature adipocytes.

    AMER DIABETES ASSOC, 2002年07月, DIABETES, 51 (7), 2045 - 2055, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Masatoshi Kawanishi, Yoshikazu Tamori, Hideki Okazawa, Satoshi Araki, Hiroaki Shinoda, Masato Kasuga

    Both syntaxin4 and VAMP2 are implicated in insulin regulation of glucose transporter-4 (GLUT4) trafficking in adipocytes as target (t) soluble N- ethylmaleimide-sensitive factor attachment protein receptors (SNARE) and vesicle (v)-SNARE proteins, respectively, which mediate fusion of GLUT4- containing vesicles with the plasma membrane. Synaptosome-associated 23-kDa protein (SNAP23) is a widely expressed isoform of SNAP25, the principal t- SNARE of neuronal cells, and colocalizes with syntaxin4 in the plasma membrane of 3T3-L1 adipocytes. In the present study, two SNAP23 mutants, SNAP23-ΔC8 (amino acids 1 to 202) and SNAP23-ΔC49 (amino acids 1 to 161), were generated to determine whether SNAP23 is required for insulin-induced translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes. Wild-type SNAP23 (SNAP23-WT) promoted the interaction between syntaxin4 and VAMP2 both in vitro and in vivo. Although SNAP23-ΔC49 bound to neither syntaxin4 nor VAMP2, the SNAP23-ΔC8 mutant bound to syntaxin4 but not to VAMP2. In addition, although SNAP23-ΔC8 bound to syntaxin4, it did not mediate the interaction between syntaxin4 and VAMP2. Moreover, overexpression of SNAP23- ΔC8 in 3T3-L1 adipocytes by adenovirus-mediated gene transfer inhibited insulin-induced translocation of GLUT4 but not that of GLUT1. In contrast, overexpression of neither SNAP23-WT nor SNAP23-ΔC49 in 3T3-L1 adipocytes affected the translocation of GLUT4 or GLUT1. Together, these results demonstrate that SNAP23 contributes to insulin-dependent trafficking of GLUT4 to the plasma membrane in 3T3-L1 adipocytes by mediating the interaction between t-SNARE (syntaxin4) and v-SNARE (VAMP2).

    2000年03月17日, Journal of Biological Chemistry, 275 (11), 8240 - 8247, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis

    J Masugi, Y Tamori, H Mori, T Koike, M Kasuga

    Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a member of the nuclear hormone receptor superfamily of transcription factors and appears to be a key regulator of adipogenesis. Members of the thiazolidinedione class of insulin-sensitizing agents act as high-affinity ligands for PPAR gamma, indicating that PPAR gamma is also important in systemic insulin action, To determine whether Pro(12) --> Ala (P12A) mutation in PPAR gamma gene contributes to the development of obesity or insulin sensitivity, we examined the effects of the P12A mutation on the function of PPAR gamma by expression of the mutant protein in COS or 3T3-L1 cells. The abilities of the P12A mutant of PPAR gamma to mediate both transcriptional activation of a luciferase reporter gene construct containing the peroxisome proliferator response element and adipogenesis induced by a thiazolidinedione drug were reduced compared with those of the wild-type protein. These results suggest that the P12A, substitution in PPAR gamma gene may be associated with abnormalities of adipose tissue formation and insulin sensitivity. (C) 2000 Academic Press.

    ACADEMIC PRESS INC, 2000年02月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 268 (1), 178 - 182, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Inhibition of adipogenesis by a COOH-terminally truncated mutant of PPAR gamma 2 in 3T3-L1 cells

    J Masugi, Y Tamori, M Kasuga

    Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that is thought to be an important regulator of adipocyte differentiation. This ligand-dependent transcription factor is also activated by thiazolidinediones, a new class of synthetic antidiabetic drugs, resulting in a marked adipogenic response in cultured cells and enhanced insulin sensitivity in vivo. The importance of the COOH-terminal region of PPAR gamma 2 in thiazolidinedione-induced adipogenesis has now been investigated by expression of a mutant protein (PPAR gamma 2-Delta C) that lacks the COOH-terminal 16 amino acids of full-length PPAR gamma 2, The mutant protein failed to bind a thiazolidinedione ligand, but its ability to bind the peroxisome proliferator response element was similar to that of the wild-type protein. Expression of PPAR gamma 2-Delta C inhibited the thiazolidinedione-induced increase in trans-activation activity of endogenous PPAR gamma in CV-1 cells. Furthermore, the mutant protein prevented thiazolidinedione-induced adipogenesis in 3T3-L1 cells, whereas expression of recombinant wildtype PPAR gamma 2 promoted adipogenesis. These data show not only that the COOH-terminal region of PPAR gamma 2 is indispensable for thiazolidinedione-induced adipogenesis mediated by this protein in 3T3-L1 cells, but also that the PPAR gamma 2-Delta C mutant acts in a dominant negative manner by interfering with the access of endogenous PPAR gamma to the peroxisome proliferator response element of target genes, (C) 1999 Academic Press.

    ACADEMIC PRESS INC, 1999年10月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 264 (1), 93 - 99, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Yoshikazu Tamori, Masatoshi Kawanishi, Toshiharu Niki, Hiroaki Shinoda, Satoshi Araki, Hideki Okazawa, Masato Kasuga

    Insulin induces the translocation of vesicles containing the glucose transporter GLUT4 from an intracellular compartment to the plasma membrane in adipocytes. SNARE proteins have been implicated in the docking and fusion of these vesicles with the cell membrane. The role of Munc18c, previously identified as an n-Sec1/Munc18 homolog in 3T3-L1 adipocytes, in insulin- regulated GLUT4 trafficking has now been investigated in 3T3-L1 adipocytes. In these cells, Munc18c was predominantly associated with syntaxin4, although it bound both syntaxin2 and syntaxin4 to similar extents in vitro. In addition, SNAP-23, an adipocyte homolog of SNAP-25, associated with both syntaxins 2 and 4 in 3T3-L1 adipocytes. Overexpression of Munc18c in 3T3-L1 adipocytes by adenovirus-mediated gene transfer resulted in inhibition of insulin-stimulated glucose transport in a virus dose-dependent manner (maximal effect, ~50%) as well as in inhibition of sorbitol-induced glucose transport (by ~35%), which is mediated by a pathway different from that used by insulin. In contrast, Munc18b, which is also expressed in adipocytes but which did not bind to syntaxin4, had no effect on glucose transport. Furthermore, overexpression of Munc18c resulted in inhibition of insulin- induced translocation of GLUT4, but not of that of GLUT1, to the plasma membrane. These results suggest that Munc18c is involved in the insulin- dependent trafficking of GLUT4 from the intracellular storage compartment to the plasma membrane in 3T3-L1 adipocytes by modulating the formation of a SNARE complex that includes syntaxin4.

    1998年07月31日, Journal of Biological Chemistry, 273 (31), 19740 - 19746, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Takanori Kubota, Hiroyuki Mori, Yoshikazu Tamori, Hideki Okazawa, Tsuneo Fukuda, Masatoshi Miki, Chikako Ito, Christophe Fleury, Frédéric Bouillaud, Masato Kasuga

    Uncoupling protein 2 (UCP2), a member of the family of mitochondrial carrier proteins, has been implicated in the control of whole-body energy balance. The coding region of the human UCP2 gene has now been shown to comprise six exons, and the sequences of the exon-intron boundaries were determined. With the use of this sequence information, 25 Japanese patients with obesity and noninsulin-dependent diabetes mellitus (NIDDM) and 25 subjects with simple obesity were screened for mutations in the entire coding region of UCP2 by PCR and single-strand conformation polymorphism analysis. Two nucleotide polymorphisms resulting in Ala55 → Val and Ala232 → Thr substitutions were detected. With the use of PCR and restriction fragment length polymorphism analysis, the allele frequencies for each of these polymorphisms were determined in 210 Japanese patients with NIDDM, 42 obese individuals, and 218 normal control subjects. The frequency of the Va155 allele did not differ significantly among the NIDDM group (46.0%), the obesity group (48.8%), and the normal control group (48.4%). The Thr232 allele was detected in only three subjects, who were heterozygotes and in the NIDDM group (allele frequency, 0.7%). However, expression in yeast of the human wild-type UCP2 protein and UCP2 containing Thr232 revealed no difference in functional activity. These results indicate that the Ala55 → Val and Ala232 → Thr variants of UCP2 do not play an important role in the pathogenesis of NIDDM or obesity in the Japanese population.

    1998年, Journal of Clinical Endocrinology and Metabolism, 83 (8), 2800 - 2804, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Satoshi Araki, Yoshikazu Tamori, Masatoshi Kawanishi, Hiroaki Shinoda, Jiro Masugi, Hiroyuki Mori, Toshiharu Niki, Hideki Okazawa, Takanori Kubota, Masato Kasuga

    SNARE proteins have been implicated in the insulin induced translocation of vesicles containing the GLUT4 glucose transporter to the plasma membrane of adipocytes. The role of the target SNARE SNAP-25 or its homologs in this process was investigated by screening a mouse adipocyte cDNA library with rat SNAP-25 and human SNAP-23 cDNA probes. Both positive clones isolated encoded a protein with 87% sequence identity to human SNAP-23, and which was therefore designated mouse SNAP-23. Immunoblot and immunofluorescence analyses revealed that SNAP-23 is located predominantly in the plasma membrane of 3T3-L1 adipocytes incubated in the absence or presence of insulin. Of syntaxins 1 to 5, SNAP-23 bound with the highest affinity to syntaxins 1 and 4 in the yeast two-hybrid system. Expression of SNAP-23, syntaxin 4, and the syntaxin-binding protein Munc18c in COS cells revealed that Munc18c reduced the amount of SNAP-23 bound to syntaxin 4 in a concentration-dependent manner. These results suggest that the binding of SNAP-23 to syntaxin 4 is inhibited by Munc18c in adipocytes.

    Academic Press Inc., 1997年05月08日, Biochemical and Biophysical Research Communications, 234 (1), 257 - 262, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Hideki Okazawa, Hiroyuki Mori, Yoshikazu Tamori, Satoshi Araki, Toshiharu Niki, Jiro Masugi, Masatoshi Kawanishi, Takanori Kubota, Hiroaki Shinoda, Masato Kasuga

    American Diabetes Association Inc., 1997年, Diabetes, 46 (11), 1904 - 1906, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Satoshi Araki, Jing Yang, Mitsuru Hashiramoto, Yoshikazu Tamori, Masato Kasuga, Geoffrey D. Holman

    The glucose transporter isoform, GLUT4, has been expressed in Chinese hamster ovary clones and its subcellular trafficking has been determined following labelling at the cell surface with the impermeant bis-mannose photolabel, 2-N-(1-azi-2,2,2-trifluoroethyl) benzoyl-1,3-bis(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA). ATB-BMPA-tagged GLUT4 leaves the cell surface rapidly and equilibrates to give an internal/surface distribution ratio of approx. 3.5 after 60 min. GLUT4 in which the N-terminal phenylalanine-5 and glutamine-6 are mutated to alanine N-(FQ-AA) and in which the C-terminal leucine-489 and -490 are mutated to alanine C-(LL-AA) have low internal/surface ratios of 0.64 and 1.24 respectively. If all cell-surface transporters are able to recycle, as would be the case for a two-pool recycling model with a single intracellular pool, then analysis suggests that the wild-type GLUT4 distribution ratio is dependent on endocytosis and exocytosis rate constants of 0.074 and 0.023 min-1. These values are similar, but not identical, to those found for GLUT4 trafficking in adipocytes. The distribution of the N-(FQ-AA) transporter appears to be due to a decrease in endocytosis with reduced intracellular retention, while the distribution of the C-(LL-AA) transporter appears to be mainly due to poor intracellular retention. These results are also considered in terms of a consecutive intracellular pool model in which GLUT4 targeting domains alter the distribution between recycling endosomes and a slowly recycling compartment. In this case the more rapid apparent exocytosis of the mutated GLUT4s is due to their failure to reach a slowly recycling compartment with a consequent return to the plasma membrane by default. It is suggested that overexpression of transporters increases the proportion that are recycled in this way. Wortmannin is shown to decrease glucose transport activity and cell-surface photolabelled transporters in a manner consistent with an inhibition of transporter recycling. Studies on the rate of loss of transport activity and ATB-BMPA-tagged transporter in wortmannin-treated cells confirm that the N-(FQ-AA) mutant is endocytosed more slowly than the wild-type GLUT4. Taken together, these results suggest that mutation at either the N- or the C-terminal domain can reduce movement to a slowly recycling intracellular compartment but that neither domain alone is entirely sufficient to produce wild-type GLUT4 trafficking behaviour.

    Portland Press Ltd, 1996年04月01日, Biochemical Journal, 315 (1), 153 - 159, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Cleavage of vesicle-associated membrane protein (VAMP)-2 and cellubrevin on GLUT4-containing vesicles inhibits the translocation of GLUT4 in 3T3-L1 adipocytes

    Y Tamori, M Hashiramoto, S Araki, Y Kamata, M Takahashi, S Kozaki, M KAsuga

    We have identified VAMP isoforms, VAMP-2 and cellubrevin, on GLUT4-containing vesicle membranes isolated from 3T3-L1 adipocytes. These proteins translocate from a low density microsomal fraction to the plasma membrane upon insulin stimulation in a fashion similar to GLUT4. VAMP-1 was not detected in this low density microsomal fraction nor on purified GLUT4-containing vesicles. In streptolysin-O permeabilized 3T3-L1 adipocytes, both VAMP-2 and cellubrevin were cleaved with botulinum neurotoxin isoform B, BoNTx/B. In addition, BoNTx/B partially inhibited insulin-stimulated GLUT4 translocation and glucose transport activity. We conclude that the synaptobrevin isoforms are important components of the insulin-dependent translocation of GLUT4 to the cell surface in adipocytes. (C) 1996 Academic Press, Inc.

    ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 1996年03月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 220 (3), 740 - 745, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Toshiharu Niki, Hiroyuki Mori, Yoshikazu Tamori, Miyako Kishimoto-Hashiramoto, Hirohisa Ueno, Satoshi Araki, Jiro Masugi, Nitin Sawant, Hemali R. Majithia, Nadeem Rais, Mitsuru Hashiramoto, Hiroshi Taniguchi, Masato Kasuga

    The mouse obese (ob) gene has recently been isolated through the positional cloning technique and has been proved to result in the obese and NIDDM phenotype in mice when mutated (Nature 372:425-432, 1994). More recently, it has been demonstrated, by experiments with recombinant ob protein, that ob gene product can cause mice, including ob/ob mice, diet- induced obesity mice, and normal mice, to lower their food intake and body weight (Science 269:540-549, 1995). To investigate the genetic and/or environmental influences underlying the development of NIDDM associated with obesity, we isolated and partially sequenced the human obese (OB) gene. The human OB gene isolated in this study encoded 167 amino acids and its open reading frame was revealed to be divided into two parts with an intermediate intron of ~2.4 kb. Using the single-strand conformation polymorphism (SSCP) technique, we screened Japanese and Asian Indian subjects for mutations in the protein coding regions of the OB gene. A total of 75 NIDDM patients with obesity (54 Japanese and 21 Asian Indians), 40 NIDDM patients without obesity (34 Japanese and 6 Asian Indians), and 34 Japanese patients with simple obesity showed no abnormal SSCP patterns in either component of the coding sequences. These results suggested that mutations in the coding regions of the OB gene are not likely to be commonly identifiable and that there would likely be a kind of obesity-associated NIDDM not caused by mutations of the OB gene.

    American Diabetes Association Inc., 1996年, Diabetes, 45 (5), 675 - 678, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Substitution of tyrosine 293 of GLUT1 locks the transporter into an outward facing conformation

    Hiroyuki Mori, Mitsuru Hashiramoto, Avril E. Clark, Jing Yang, Akihiro Muraoka, Yoshikazu Tamori, Masato Kasuga, Geoffrey D. Holman

    Tyrosines 292 and 293 in the mammalian glucose transporter GLUT1 have been substituted by either isoleucine or phenylalanine. Chinese hamster ovary clones that were transfected with Tyr-292 → Ile, Tyr-292 → Phe, Tyr-293 → Ile, and Tyr-293 → Phe constructs of GLUT1 were shown, by Western blotting and cell surface carbohydrate labeling, to have expression levels that were comparable with the wild type. The V(max) for 2-deoxy-D-glucose transport was markedly reduced only as a result of the Tyr-293 → Ile mutation. The ability of the Tyr-293 → Ile mutated GLUT1 to bind the exofacial ligand 2-N-4-(1- azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA) and the endofacial ligand cytochalasin B were assessed by photolabeling procedures. The ability to bind the bis-mannose compound was unimpaired, whereas the ability to bind cytochalasin B was totally abolished, and the level of labeling was lower than in the nontransfected clone. Affinities of the wild-type and Tyr-293 → Ile GLUT1 for D-glucose, the exofacial ligands (ATB-BMPA and 4,6-O-ethylidene-D-glucose), and the endofacial ligand (cytochalasin B) were assessed by the ability of these agents to displace the radioactive ATB-BMPA photolabel. These data indicated that the Tyr-293 → Ile substitution produced no change in the affinity for D-glucose, a relatively small enhancement in the affinity for exofacial ligands, but a large ≃300-fold reduction in affinity for cytochalasin B, suggesting that the mutated GLUT1 is locked in an outward facing conformation. The observation that the Tyr-293 → Ile mutant transporter can bind nontransported C4 and C6 substituted hexose analogues but cannot catalyze transport is interpreted as indicating that Tyr-293 is involved in closing the exofacial site around C4 and C6 of D-glucose in the transport catalysis process.

    1994年04月15日, Journal of Biological Chemistry, 269 (15), 11578 - 11583, 英語

    [査読有り]

    研究論文(学術雑誌)

  • SUBSTITUTION AT PRO(385) OF GLUT1 PERTURBS THE GLUCOSE-TRANSPORT FUNCTION BY REDUCING CONFORMATIONAL FLEXIBILITY

    Y TAMORI, M HASHIRAMOTO, AE CLARK, H MORI, A MURAOKA, T KADOWAKI, GD HOLMAN, M KASUGA

    The mammalian glucose transporter, GLUT1, is capable of alternating between two conformations which expose either an outward- or inward-facing ligand binding site. The possibility that these conformational changes are related to the presence of prolines and glycines in transmembrane region 10 was investigated by site-directed mutagenesis. Chinese hamster ovary clones which were transfected with Pro385 --> Ile and Pro385 --> glycine mutations of GLUT1 were shown, by Western blotting and cell surface carbohydrate labeling, to have expression levels which were comparable with the wild type. The transport activity was markedly reduced as a result of the Pro385 --> isoleucine but not in the Pro385 --> glycine mutation. The loss of transport activity in the Pro385 --> isoleucine clone was associated with loss of labeling by the exofacial photoaffinity ligand, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4-yloxy)-2-propylamine (ATB-BMPA), but there was no loss in labeling by the inside site-directed ligand cytochalasin B. These results suggest that the transporter cannot adopt the outward-directed conformation in the Pro385 --> isoleucine clone. By contrast, the glycine substitution for proline at this position resulted in a retention of the ligand binding properties at both inside and outside sites. We suggest a putative mode of operation of the transporter which involves conformational flexibility about the prolines in transmembrane segment 10 such that helices 11 and 12 can alternately either pack against the outside (ATB-BMPA binding) site in helices 7, 8, and 9 or against the inner (cytochalasin B binding) site at the base of transmembrane segment 10.

    AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 1994年01月, JOURNAL OF BIOLOGICAL CHEMISTRY, 269 (4), 2982 - 2986, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Normal insulin receptor substrate-1 phosphorylation in autophosphorylation-defective truncated insulin receptor. Evidence that phosphorylation of substrates might be sufficient for certain biological effects evoked by insulin

    R. Yamamoto-Honda, T. Kadowaki, K. Momomura, K. Tobe, Y. Tamori, Y. Shibasaki, Y. Mori, Y. Kaburagi, O. Koshio, Y. Akanuma, Y. Yazaki, M. Kasuga

    A mutant human insulin receptor that lacked the 82 amino acids of the COOH terminus of the β-subunit (del82) was studied. Both the wild type insulin receptor (HIR) and the mutant receptor were expressed in Chinese hamster ovary (CHO) cells by stable transfection. Autophosphorylation and tyrosine kinase activities toward exogenous substrates of solubilized and partially purified del82 were severely impaired. When CHO cells transfected with del82 (CHO-del82) were stimulated with insulin, autophosphorylation was decreased to a great extent compared with cells expressing HIR (CHO-HIR). Nevertheless, tyrosine phosphorylation of an endogenous substrate, pp185, and insulin receptor substrate-1 (IRS-1) in CHO-del82 was comparable with that in CHO- HIR. Insulin-stimulated activation of phosphatidylinositol 3-kinase activity in CHO-del82 was also equivalent to that in CHO-HIR. Moreover, CHO-del82 exhibited the same insulin sensitivity as CHO-HIR with respect to 2- deoxyglucose uptake and thymidine incorporation into DNA. Insulin-induced internalization in CHO-del82 was decreased by 46% as compared with that in CHO-HIR. These data suggest that: 1) the COOH-terminal domain of the insulin receptor may play an inhibitory role in the phosphorylation of pp185 and IRS- 1 and 2) phosphorylation of substrates such as pp185 and IRS-1, rather than autophosphorylation of the receptor per se, correlates better with certain biological effects that were mediated by insulin, suggesting that phosphorylation of the substrates might be sufficient for transducing signals downstream.

    1993年, Journal of Biological Chemistry, 268 (22), 16859 - 16865, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Enhanced insulin-induced mitogenesis and mitogen-activated protein kinase activities in mutant insulin receptors with substitution of two COOH-terminal tyrosine autophosphorylation sites by phenylalanine

    A. Ando, K. Momomura, K. Tobe, R. Yamamoto-Honda, H. Sakura, Y. Tamori, Y. Kaburagi, O. Koshio, Y. Akanuma, Y. Yazaki, M. Kasuga, T. Kadowaki

    We have studied the function of a mutant human insulin receptor in which two COOH-terminal autophosphorylation sites (Tyr-1316 and -1322) were replaced by phenylalanine (F/Y COOH-terminal 2 tyrosines (CT2)). In addition, we have also constructed a mutant receptor in which Lys-1018 in the ATP-binding site was changed to arginine (R/K 1018). Both the wild type insulin receptor (HIR) and the mutant receptors were expressed in Chinese hamster ovary (CHO) cells by stable transfection. Autophosphorylation of solubilized and partially purified F/Y CT2 was decreased by approximately 30% compared with the HIR. Tyrosine kinase activities of F/Y CT2 and HIR toward exogenous substrates were almost equal. When CHO cells transfected with F/Y CT2 (CHO-F/Y CT2) were stimulated with insulin, autophosphorylation of the β-subunit of the insulin receptor and the phosphorylation of an endogenous substrate (pp185) in the intact cell were normal compared with cells expressing HIR (CHO-HIR). CHO-F/Y CT2 exhibited the same insulin sensitivity as CHO-HIR with respect to 2-deoxyglucose uptake. However, the dose-response curve of insulin-stimulated thymidine incorporation in CHO-F/Y CT2 was shifted to the left (~5-7-fold) compared with that in CHO-HIR. There was no significant difference in insulin-like growth factor 1-stimulated thymidine incorporation between CHO-F/Y CT2 and CHO-HIR. Furthermore, the dose-response curve of insulin-stimulated kinase activity toward myelin basic protein in CHO-F/Y CT2 was also shifted to the left (~5-fold) compared with that in CHO-HIR. Kinase assays in myelin basic protein-containing gels revealed that both species of MAP kinases (M(r) 44,000, 42,000) were more sensitive to activation by insulin in CHO-F/Y CT2 than in CHO-HIR. This observation was confirmed in immune complex kinase assays toward microtubule-associated protein 2 (MAP2) using specific antibodies against mitogen-activated protein (MAP) kinase. R/K 1018 mutant insulin receptors showed an absence of insulin-stimulated kinase activity and CHO cells transfected with R/K 1018 (CHO-R/K 1018) failed to enhance 2- deoxyglucose uptake or thymidine incorporation in response to insulin. In addition, R/K 1018 kinase-defective insulin receptors were unable to mediate insulin-stimulated MAP kinase activation. These data suggest that: 1) tyrosine kinase activity of the insulin receptor is required for activation of insulin-stimulated MAP kinases and 2) phosphorylation of COOH-terminal tyrosine residues may play an inhibitory role in mitogenic signaling through regulation of MAP kinases.

    1992年, Journal of Biological Chemistry, 267 (18), 12788 - 12796, 英語

    [査読有り]

    研究論文(学術雑誌)

MISC

  • SS-MIX2を活用した診療録直結型肥満症データベース(J-ORBIT)の構築と収集情報の分析

    中川靖, 廣田勇士, 浜口哲矢, 松岡敦子, 竹内健人, 高吉倫史, 山本あかね, 坂口一彦, 田守義和, 石井雅通, 美代賢吾, 前田英一, 小川渉

    2020年, 糖尿病(Web), 63 (Suppl)

  • 【糖尿病とがん】 糖尿病における発がんリスク上昇のメカニズム

    西本祐希, 田守義和, 小川渉

    2019年01月, 医薬ジャーナル, 55 (1号), 71 - 76, 日本語

    [招待有り]

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • 【糖尿病とがんを解きほぐす-臨床・基礎・疫学が織りなす両者の関係-】 糖尿病とがんの接点 肥満とインスリン抵抗性

    田守義和, 小川渉

    2018年09月, プラクティス, 35 (5号), 516 - 521, 日本語

    [招待有り]

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • 【エネルギー代謝調節研究の新展開】 褐色脂肪細胞が多房性の小脂肪滴を形成して効率よくエネルギー消費を行うメカニズム

    西本祐希, 田守義和

    2017年06月, 内分泌・糖尿病・代謝内科, 44 (6号), 438 - 442, 日本語

    [招待有り]

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • 【マクロファージ・樹状細胞と機能制御】 大腸の炎症性マクロファージがCcl2-Ccr2依存性に全身のインスリン抵抗性をひき起こす

    川野義長, 中江淳, 渡辺信之, 菊地徹洋, 楯谷三四郎, 田守義和, 金子麻里, 阿部高也, 小野寺雅史, 伊藤裕

    2017年05月, 臨床免疫・アレルギー科, 67 (5号), 466 - 470, 日本語

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • Yuki Nishimoto, Yoshikazu Tamori

    White adipose tissue (WAT) stores energy as triacylglycerol in preparation for fasting state. In contrast, brown adipose tissue (BAT) consumes energy and produces heat in a cold environment. One of the major differences between these two adipose tissues is the morphology of the intracellular lipid droplet (LD), which is large and unilocular in WAT and small and multilocular in BAT. Although the fat-specific protein 27 alpha (FSP27α), belonging to the cell death-inducing DNA fragmentation factor A (DFFA)-like effector (Cide) family, was known to be indispensable for large unilocular LD formation in WAT, the mechanism that regulated small multilocular LD formation in BAT remained unknown. We recently uncovered that FSP27β, a novel isoform of FSP27 abundantly expressed in BAT, plays a crucial role in small multilocular LD formation by inhibiting the homodimerization of CideA in BAT. We speculate that unilocular LD formation is ideal for efficient lipid storage in WAT because lipolysis from the LD surface is restricted due to the minimum LD surface area. In addition, hydrolyzed free fatty acid (FFA) and glycerol can efficiently flow out into the circulation from the cell surface. In contrast, small multilocular LD formation is ideal for efficient intracellular lipolysis from the LD surface and the subsequent facilitation of FFA transport to mitochondria that are adjacent to LDs for β-oxidation in BAT. Thus, intracellular LD morphology is closely related to the functions and characteristics of adipose tissues. Given that the browning of adipose tissue leads to enhanced energy expenditure and the prevention of obesity, clarification of the mechanism with respect to intracellular LD formation is very meaningful.

    Japan Atherosclerosis Society, 2017年, Journal of Atherosclerosis and Thrombosis, 24 (10), 989 - 998, 英語

    書評論文,書評,文献紹介等

  • Colon Macrophage Regulates Insulin Sensitivity under High-Fat Diet

    Jun Nakae, Yoshinaga Kawano, Nobuyuki Watanabe, Tetsuhiro Kikuchi, Sanshiro Tateya, Yoshikazu Tamori, Noriko Kodani, Nobuko Goto, Motoko Matsuzaki, Lisa Ohira, Ayako Shigeta, Masashi Onodera, Masato Kasuga, Hiroshi Itoh

    AMER DIABETES ASSOC, 2015年06月, DIABETES, 64, A539 - A539, 英語

    研究発表ペーパー・要旨(国際会議)

  • 【最新肥満症学-基礎・臨床研究の最前線-】 肥満・肥満症の病態生理

    田守義和, 春日雅人

    2014年05月, 日本臨床, 72 (増刊4 最新肥満症学), 7 - 12, 日本語

    [招待有り]

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • Recent advances in obesity-induced inflammation and insulin resistance

    TateyaS, KimF, TamoriY

    2013年08月, Front Endocrinol (Lausanne), 4, 93, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • Yoshikazu Tamori

    2013年06月, Diabetology International, 4 (2), 97 - 100, 英語

    速報,短報,研究ノート等(学術雑誌)

  • Glypican-4 is a new comer of adipokines working as insulin sensitizer

    TamoriY, KasugaM

    2013年05月, J Diabetes Investig, 4 (3), 250 - 1, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • 脂肪細胞の脂肪蓄積形態が制御する個体のエネルギー代謝

    田守義和

    2013年03月, 愛仁会医学研究誌, 44, 1 - 5, 日本語

    [査読有り]

    記事・総説・解説・論説等(大学・研究所紀要)

  • Progranulin(PGRN); インスリン抵抗性を誘導する新規アディポカイン

    松原 稔哉, 三田 綾子, 南 幸太郎, 細岡 哲也, 北澤 荘平, 高橋 健一, 田守 義和, 横井 伯英, 西村 紀, 清野 進

    (一社)日本糖尿病学会, 2012年04月, 糖尿病, 55 (Suppl.1), S - 114, 日本語

  • 新規アディポカインProgranulin(PGRN)の同定とインスリン抵抗性ならびに肥満における役割

    松原 稔哉, 三田 綾子, 南 幸太郎, 田守 義和, 北澤 荘平, 渡辺 真, 松尾 英一, 西村 紀, 清野 進

    (一社)日本糖尿病学会, 2011年04月, 糖尿病, 54 (Suppl.1), S - 156, 日本語

  • インスリン抵抗性の分子基盤 脂肪組織の慢性炎症の最近の動向

    田守義和

    2010年11月, 最新医学, 65 (11号), 2448 - 2453, 日本語

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • 【糖尿病の病態を「見える化」してみる どこまでわかりやすくできるか】 2型糖尿病

    田守義和

    2010年01月, 糖尿病診療マスター, 8巻, 1, pp. 25-30, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 肥満とインスリン抵抗性

    田守義和

    2009年02月, 日本臨床, 67巻, 2, pp. 236-244, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【肥満 最新の基礎・臨床研究】 総論 肥満とインスリン抵抗性

    田守義和, 春日雅人

    2009年02月, 日本臨床, 67 (2号), 236 - 244, 日本語

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • 見る脂質のページ 遺伝子操作実験動物 MCP-1/CCR2ノックアウトマウス・トランスジェニックマウス

    田守義和

    2009年01月, The Lipid, 20 (1号), 4 - 8, 日本語

    記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)

  • MCP-1/CCR2ノックアウトマウス・トランスジェニックマウス

    田守義和

    2009年01月, The Lipid, 20巻, 1, pp. 4-8, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 単球・マクロファージとエネルギー代謝調節

    田守 義和

    日本糖尿病学会, 2008年05月30日, 糖尿病 = Journal of the Japan Diabetes Society, 51 (5), 395 - 397, 日本語

  • 【臓器間クロストークによるエネルギー代謝調節】 単球・マクロファージとエネルギー代謝調節

    田守義和

    2008年05月, 糖尿病, 51巻, 5号, pp. 395-397, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【新時代の糖尿病学 病因・診断・治療研究の進歩】 糖尿病基礎研究の進歩 糖尿病と耐糖能低下の成因分類と発症機序 2型糖尿病 インスリン抵抗性にかかわる因子 MCP-1

    田守義和

    2008年05月, 日本臨床, 66巻, 増刊3 新時代の糖尿病学(1), pp. 475-, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【インスリン抵抗性と炎症】 脂肪組織と炎症 脂肪細胞肥大化と炎症

    田守 義和

    2008年02月, Diabetes Frontier, 19巻, 1号, pp. 27-31, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 糖尿病 基礎分野での進歩 炎症とインスリン抵抗性

    田守 義和

    2008年01月, Annual Review糖尿病・代謝・内分泌, 2008巻, , pp. 1-9, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • メタボリックシンドロームとインスリン抵抗性

    田守 義和

    2007年08月, 肥満研究, 13巻, 2号, pp. 124-129, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • MCP-1 can induce systemic insulin resistance in vivo without inflammation in adipose tissue

    Sanshiro Tateya, Yoshikazu Tamori, Hajime Kanda, Masato Kasuga

    AMER DIABETES ASSOC, 2007年06月, DIABETES, 56, A375 - A375, 英語

    研究発表ペーパー・要旨(国際会議)

  • 【メタボリックシンドロームup to date】 トピックス メタボリックシンドロームの分子基盤と炎症・細胞機能

    田守 義和

    2007年06月, 日本医師会雑誌, 136巻, 特別1, pp. S308-S310, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • メタボリックシンドロームの分子基盤

    田守 義和

    2007年04月, 日本消化器病学会雑誌, 104巻, 4号, pp. 483-491, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【メタボリックシンドローム】 メタボリックシンドロームの分子機構

    田守義和

    2007年02月, 血圧, 14巻, 2号, pp. 183-186, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • Metabolic Syndromeの成因・病態 Metabolic Syndromeとインスリン抵抗性

    田守義和

    2007年02月, 心臓, 39巻, 2号, pp. 190-194, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【アディポサイトカインUpdate】 @

    田守義和

    2006年11月, Adiposcience, 3巻, 3号, pp. 306-312, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【アディポカイン】 RBP4 脂肪細胞特異的GLUT4欠損マウスからあらたに同定されたユニークなアディポカイン

    田守義和

    2006年11月, 医学のあゆみ, 219巻, 6号, pp. 458-462, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【炎症とアディポサイエンス】 基礎 インスリン抵抗性と炎症

    田守義和

    2006年07月, Adiposcience, 3巻, 2号, pp. 165-172, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【メタボリックシンドローム】 メタボリックシンドロームの基礎 インスリン抵抗性発症の分子基盤

    田守義和

    2006年06月, 最新医学, 61巻, 6月増刊, pp. 1225-1236, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • インスリン抵抗性発症の分子基盤

    田守 義和

    2006年06月, 最新医学, 61巻, pp. 13-24, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【臨床に役立つ内分泌疾患診療マニュアル2006】 代謝疾患 糖尿病

    田守義和

    2006年04月, ホルモンと臨床, 54巻, 春季増刊, pp. 208-215, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 糖尿病発症の分子機構 MCP-1とメタボリックシンドローム

    田守義和

    2006年03月, 分子糖尿病学の進歩: 基礎から臨床まで, pp. 68-73, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • RBP4, an unexpected adipokine

    Yoshikazu Tamori, Hiroshi Sakaue, Masato Kasuga

    2006年01月, Nature Medicine, Vol. 12, No. 1, pp. 30-31, 英語

    記事・総説・解説・論説等(学術雑誌)

  • 【タンパク・遺伝子からみた分子病 新しく解明されたメカニズム】 受容体 PPAR-γ/peroxisome-proliferator-activated receptor-γ(PPARG)

    田守義和, 春日雅人

    2005年10月, 生体の科学, 56巻, 5号, pp.414-415, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • 【脂肪細胞,脂肪蓄積と糖代謝異常】 脂肪組織のMCP-1発現の亢進とインスリン抵抗性

    田守義和

    2005年08月, 内分泌・糖尿病科, 21巻, 2号, pp.141-146, 日本語

    記事・総説・解説・論説等(学術雑誌)

  • Increased expression of MCP-1 in adipose tissues is involved in insulin resistance in db/db mice

    H Kanda, Y Tamori, K Kotani, M Kasuga

    AMER DIABETES ASSOC, 2004年06月, DIABETES, 53, A310 - A310, 英語

    研究発表ペーパー・要旨(国際会議)

  • Minimal PKC activation-mediated inhibition of CCK-OPE stimulated enzyme secretion involves Munc18c dissociation from the acinar basolateral plasma membrane.

    HY Gaisano, J Leser, L Sheu, Y Tamori, M Kasuga, W Trimble, MP Lutz

    W B SAUNDERS CO-ELSEVIER INC, 1999年04月, GASTROENTEROLOGY, 116 (4), A1126 - A1126, 英語

    研究発表ペーパー・要旨(国際会議)

  • CLEAVAGE OF THE VESICLE-ASSOCIATED MEMBRANE-PROTEIN (VAMP)-2 ON THE GLUT4-CONTAINING VESICLES INHIBITS THE TRANSLOCATION OF GLUT4 IN 3T3-L1 ADIPOCYTES

    Y TAMORI, M HASHIRAMOTO, S ARAKI, M KASUGA

    AMER DIABETES ASSOC, 1995年05月, DIABETES, 44, A32 - A32, 英語

    研究発表ペーパー・要旨(国際会議)

書籍等出版物

  • 分子糖尿病学の進歩: 基礎から臨床まで / インスリン作用の分子機構 CIDEファミリーの機能

    田守義和

    共編者(共編著者), 金原出版, 2009年04月, 日本語

    学術書

  • 糖尿病カレントライブラリー7 / RBP4

    田守 義和

    共著, 文光堂, 2007年05月, 日本語

    学術書

  • インスリン抵抗性 / インスリン抵抗性のメカニズム(総論)

    田守 義和

    共著, 医学書医院, 2006年12月, 日本語

    学術書

  • 分子糖尿病学の進歩 / MCP-1とメタボリックシンドローム

    田守 義和

    共著, 金原出版, 2006年03月, 日本語

    学術書

  • 生活習慣病がわかる / 肥満によるインスリン抵抗性と脂肪組織の炎症

    田守 義和, 神田 一

    共著, 羊土社, 2005年, 日本語

    学術書

講演・口頭発表等

  • 肥満は万病の元〜肥満が引きおこすいろいろな病気〜

    田守 義和

    第39回日本肥満学会, 2018年10月, 日本語, 神戸, 国内会議

    公開講演,セミナー,チュートリアル,講習,講義等

  • 糖尿病治療と肥満パラドックス

    田守 義和

    第55回日本糖尿病学会近畿地方会, 2018年10月, 日本語, 神戸, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 千船病院における高度肥満・糖尿病に対する外科治療の中期成績

    北濱 誠一, 三原 俊彦, 岡田 憲幸, 山元 康義, 向井 友一郎, 広中 順也, 松山 温子, 佐藤 洋幸, 田守 義和, 高橋 哲也

    第55回日本糖尿病学会近畿地方会, 2018年10月, 日本語, 神戸, 国内会議

    ポスター発表

  • 千船病院における高度肥満・糖尿病に対する外科治療の中期成績

    北濱 誠一, 三原 俊彦, 岡田 憲幸, 山元 康義, 向井 友一郎, 広中 順也, 松山 温子, 佐藤 洋幸, 田守 義和, 高橋 哲也

    第39回日本肥満学会, 2018年10月, 日本語, 神戸, 国内会議

    ポスター発表

  • 耳鼻科領域での短期ステロイド療法中の血糖管理におけるトホグリフロジンの使用経験

    佐藤 洋幸, 広中 順也, 松山 温子, 平賀 千尋, 鞆津 匡宏, 奥西 真帆, 伊集院 隆宏, 田守 義和, 高橋 哲也

    第55回日本糖尿病学会近畿地方会, 2018年10月, 日本語, 神戸, 国内会議

    ポスター発表

  • FSP27欠損マウスの白色脂肪細胞ではオートファジーの亢進が脂肪分解に寄与する

    中島 進介, 岩橋 泰幸, 西本 祐希, 楯谷 三四郎, 小川 渉, 田守 義和

    第39回日本肥満学会, 2018年10月, 日本語, 神戸, 国内会議

    ポスター発表

  • FSP27欠損マウスの白色脂肪組織ではオートファジーの亢進が脂肪分解に寄与する

    中島 進介, 西本 祐希, 楯谷 三四郎, 岩橋 泰幸, 小川 渉, 田守 義和

    第23回アディポサイエンス・シンポジウム, 2018年08月, 日本語, 大阪, 国内会議

    ポスター発表

  • 脂肪細胞特異的インスリン作用不全モデルを用いたNASHの分子メカニズムの解明

    細岡 哲也, 松木 核, 篠原 正和, 千賀 陽子, 田守 義和, 松居 翔, 佐々木 努, 北村 忠弘, 黒田 雅士, 阪上 浩, 伊藤 義人, 山口 寛二, 中江 淳, 春日 雅人, 小川 渉

    第5回肝臓と糖尿病・代謝研究会, 2018年07月, 日本語, 米子, 国内会議

    口頭発表(一般)

  • 腹腔鏡下スリーブ状胃切除術により糖尿病が寛解した一例

    松下和子, 北濱 誠一, 三原 俊彦, 広中 順也, 井上 真希, 佐藤 洋幸, 田守 義和, 高橋 哲也

    第61回日本糖尿病学会年次学術集会, 2018年05月, 日本語, 東京, 国内会議

    ポスター発表

  • 多房性脂肪滴蓄積を示すFSP27欠損マウスの白色脂肪細胞ではオートファジーの亢進が脂肪分解に寄与する

    中島 進介, 岩橋 泰幸, 西本 祐希, 楯谷 三四郎, 小川 渉, 田守 義和

    第61回日本糖尿病学会年次学術集会, 2018年05月, 日本語, 東京, 国内会議

    ポスター発表

  • 高度肥満に腹腔鏡下胃スリーブ切除術を行い全ての糖尿病治療薬を中止できた緩徐進行1型糖尿病の1例

    広中 順也, 北濱 誠一, 井上 真希, 佐藤 洋幸, 高橋 哲也, 田守 義和

    第61回日本糖尿病学会年次学術集会, 2018年05月, 日本語, 東京, 国内会議

    ポスター発表

  • 血糖コントロール不良なインスリン使用2型糖尿病患者に対するデュラグルチドとエンパグリフロジンの追加効果の検討

    佐藤 洋幸, 井上 真希, 広中 順也, 高橋 哲也, 田守 義和

    第61回日本糖尿病学会年次学術集会, 2018年05月, 日本語, 東京, 国内会議

    ポスター発表

  • メタボリックサージェリー〜糖尿病の重症度に応じた術式選択〜

    北濱 誠一, 三原 俊彦, 岡田 憲幸, 山元 康義, 向井 友一郎, 広中 順也, 井上 真希, 佐藤 洋幸, 田守 義和, 高橋 哲也

    第61回日本糖尿病学会年次学術集会, 2018年05月, 日本語, 東京, 国内会議

    ポスター発表

  • Role of the small GTPase Rac1 in insulin-dependent glucose uptake in skeletal muscle cells.

    上田修司, 田守義和, 饗場篤, 片岡徹, 佐藤孝哉

    神戸大学グローバルCOEプログラム「統合的膜生物学の国際教育研究拠点」 第3回ワークショップ, 2009年07月, 英語, 神戸大学/グローバルCOE, 淡路, 国際会議

    ポスター発表

  • 2型糖尿病患者の初回受診前後の食事摂取状況に関する検討

    廣田勇士, 田守義和, 坂口一彦, 宮脇郁子

    第51回日本糖尿病学会年次学術集会, 2007年05月, 日本語, 日本糖尿病学会, 仙台, 国内会議

    ポスター発表

  • 治療開始直後の2型糖尿病患者の食事摂取量とその自己評価に関する検討

    廣田勇士, 田守義和, 坂口一彦, 宮脇郁子

    第52回日本糖尿病学会年次学術集会, 2007年05月, 日本語, 日本糖尿病学会, 仙台, 国内会議

    ポスター発表

  • 2型糖尿病患者のコントロール指標に影響する身体活動

    傳 秋光, 田守 義和, 野口 哲也, 木戸 良明, 大原 毅, 小川 渉, 宮脇 郁子

    第50回日本糖尿病学会年次学術集会, 2007年05月, 日本語, 日本糖尿病学会, 仙台, 国内会議

    口頭発表(一般)

  • 2型糖尿病患者におけるBMIおよび歩数別の食事摂取量と食事自己管理行動の特徴、

    傳秋光, 田守義和, 野口哲也, 木戸良明, 大原毅, 小川渉, 宮脇郁子

    第50回日本糖尿病学会年次学術集会, 2007年05月, 日本語, 日本糖尿病学会, 仙台, 国内会議

    ポスター発表

  • 2型糖尿病患者におけるBMIおよび歩数別の食事摂取量と食事自己管理行 動の特徴

    傳秋光, 田守義和, 野口哲也, 木戸良明, 大原毅, 小川渉, 宮脇郁子

    第50回日本糖尿病学会年次学術集会, 2007年05月, 日本語, 日本糖尿病学会, 仙台, 国内会議

    口頭発表(一般)

  • MCP-1 contributes to macrophage infiltration of adipose tissues, insulin resistance and hepatic steatosis in obesity.

    神田 一, 田守 義和, 小谷 光, 楯谷 三四郎, 春日 雅人

    キーストンシンポジウム2006, 2006年01月, 英語, キーストンシンポジウム, バンクーバー, 国際会議

    ポスター発表

  • MCP-1 contributes to macrophage infiltration into adipose tissue,insulin resistance and hepatic steatosis in obesity

    楯谷 三四郎, 田守 義和, 神田 一, 小谷 光, 春日 雅人

    第7回インスリン作用シンポジウム, 2005年10月, 英語, インスリン作用シンポジウム事務局, 熊本, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • MCP-1 links obesity to insulin resistance.

    田守 義和, 神田 一, 小谷 光, 楯谷 三四郎, 春日 雅人

    1st Scientific Meeting of the Asia-Pacific Diabetes and Obesity Study Group, 2005年08月, 英語, 神戸, 国際会議

    ポスター発表

  • Increased Expression of MCP-1 in Adipose Tissues is Involved in Insulin Resistance Induced by Obesity.

    田守 義和, 神田 一, 小谷 光, 楯谷 三四郎, 春日 雅人

    第10回アディポサイエンスシンポジウム, 2005年08月, 英語, アディポサイエンスシンポジウム事務局, 大阪, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • 肥満マウスの脂肪組織および血中で増加したMCP-1は肝臓でのインスリン抵抗性に関与する

    神田 一, 田守 義和, 小谷 光, 楯谷 三四郎, 春日 雅人

    第78回日本内分泌学会総会, 2005年07月, 日本語, 日本内分泌学会, 東京, 国内会議

    口頭発表(一般)

  • 脂肪組織で発現増加するMCP-1のインスリン抵抗性に及ぼす病態的意義

    田守 義和, 神田 一, 楯谷 三四郎, 春日 雅人

    日本臨床分子医学会42回学術総会, 2005年07月, 日本語, 日本臨床分子医学会, 京都, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • 肥満マウスの脂肪組織および血中で増加したMCP-1は個体レベルで肝臓でのインスリン抵抗性に関与する

    神田 一, 田守 義和, 小谷 光, 楯谷 三四郎, 春日 雅人

    第48回日本糖尿病学会年次学術集会, 2005年05月, 日本語, 日本糖尿病学会, 神戸, 国内会議

    口頭発表(一般)

  • Increased expression of MCP-1 in adipose tissues is involved in insulin resistance of db/db mice

    田守 義和, 神田 一, 小谷 光, 楯谷 三四郎, 春日 雅人

    9th International Symposium On Insulin Receptors and Insulin Action, 2004年10月, 英語, 国際インスリン受容体作用シンポジウム事務局, ニース, 国際会議

    口頭発表(一般)

  • 肥満マウスの脂肪組織および血中で増加したMCP-1は肝臓でのインスリン抵抗性に関与する

    神田 一, 田守 義和, 小谷 光, 楯谷 三四郎, 日浅 謙一, 江頭 健輔, 春日 雅人

    第25回日本肥満学会, 2004年09月, 日本語, 日本肥満学会, 大阪, 国内会議

    口頭発表(一般)

  • Negative role for Munc18c in insulin-stimulated externalization of GLUT4 in a wortmannin-sensitive manner.

    神田 一, 田守 義和, 篠田 昭弘, 吉川 真理, 坂上 元祥, 宇田川 潤, 大谷 浩, 田代 文, 宮崎 純一, 春日 雅人

    第6回インスリン作用シンポジウム, 2004年09月, 英語, インスリン作用シンポジウム事務局, 京都, 国際会議

    ポスター発表

  • 内分泌代謝学と生活習慣病 肥満マウスの脂肪組織におけるMCP-1発現の亢進はインスリン抵抗性の発症に関与する

    田守 義和, 神田 一, 小谷 光, 楯谷 三四郎, 春日 雅人

    第77回日本内分泌学会総会, 2004年06月, 日本語, 日本内分泌学会, 京都, 国内会議

    [招待有り]

    口頭発表(招待・特別)

  • Increased Expression of MCP-1 in Adipose Tissues Is Involved in Insulin Resistance in db/db Mice

    神田 一, 田守 義和, 小谷 光, 楯谷 三四郎, 春日 雅人

    第64回米国糖尿病学会, 2004年06月, 英語, 米国糖尿病学会, オーランド, 国際会議

    ポスター発表

  • Munc18cはインスリン依存性GLUT4小胞の細胞膜への移行には影響を与えずにGLUT4小胞の細胞膜への融合を抑制する

    神田 一, 田守 義和, 篠田 昭弘, 吉川 真理, 坂上 元祥, 宇田川 潤, 大谷 浩, 田代 文, 宮崎 純一, 春日 雅人

    第47回日本糖尿病学会年次学術集会, 2004年05月, 日本語, 日本糖尿病学会, 東京, 国内会議

    口頭発表(一般)

  • 3T3-L1脂肪細胞におけるcortical actin networkのGLUT4 translocationに対する機能解析

    吉川 真理, 田守 義和, 神田 一, 春日 雅人

    第47回日本糖尿病学会年次学術集会, 2004年05月, 日本語, 日本糖尿病学会, 東京, 国内会議

    口頭発表(一般)

  • Loss of Munc18c enhances insulin-stimulated GLUT4 externalization to cell surface but not traffic to plasma membrane in adipocytes

    神田 一, 田守 義和, 篠田 昭弘, 吉川 真理, 坂上 元祥, 宇田川 潤, 大谷 浩, 田代 文, 宮崎 純一, 春日 雅人

    キーストンシンポジウム2004, 2004年03月, 英語, キーストンシンポジウム, バンフ, 国際会議

    ポスター発表

  • Syntaxin4結合蛋白Munc18cはインスリン依存性GLUT4の細胞膜への移行には影響を与えないが細胞表面への露出に対しては抑制的に機能する

    神田 一, 田守 義和, 篠田 昭弘, 春日 雅人

    日本分子生物学学会第26回年会, 2003年12月, 日本語, 日本分子生物学学会, 神戸, 国内会議

    口頭発表(一般)

  • Loss of Munc18c enhances insulin-stimulated GLUT4 externalization to cell surface but not traffic to plasma membrane in adipocytes

    神田 一, 田守 義和, 篠田 昭弘, 吉川 真理, 坂上 元祥, 宇田川 潤, 大谷 浩, 田代 文, 宮崎 純一, 春日 雅人

    第5回インスリン作用シンポジウム, 2003年10月, 英語, インスリン作用シンポジウム事務局, 東京, 国際会議

    [招待有り]

    口頭発表(招待・特別)

  • Loss of Munc18c Results in Decrease of Syntaxin4 Protein without Inhibiting Insulin-Stimulated GLUT4 Translocation in Adipocytes

    神田 一, 田守 義和, 篠田 昭弘, 吉川 真理, 坂上 元祥, 宇田川 潤, 大谷 浩, 田代 文, 宮崎 純一, 春日 雅人

    第63回米国糖尿病学会, 2003年06月, 英語, 米国糖尿病学会, ニューオーリンズ, 国際会議

    ポスター発表

  • 脂肪細胞でのGLUT4トランスロケーションに対するsyntaxin4結合蛋白Munc18cの機能解析

    神田 一, 田守 義和, 篠田 昭弘, 春日 雅人

    第46回日本糖尿病学会年次学術集会, 2003年05月, 日本語, 日本糖尿病学会, 富山, 国内会議

    口頭発表(一般)

所属学協会

  • アジア糖尿病学会

    2010年02月
  • 日本病態栄養学会

    2009年08月 - 現在
  • 日本肥満学会

    2008年12月 - 現在
  • 日本内分泌学会

    2007年04月 - 現在
  • 日本消化器病学会

  • 日本糖尿病学会

  • 日本内科学会

共同研究・競争的資金等の研究課題