研究者紹介システム

淺原 俊一郎
アサハラ シュンイチロウ
医学部附属病院 糖尿病・内分泌内科
助教
医学
Last Updated :2022/04/15

研究者情報

所属

  • 【主配置】

    医学部附属病院 糖尿病・内分泌内科
  • 【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

研究ニュース

研究活動

研究分野

  • ライフサイエンス / 代謝、内分泌学
  • ライフサイエンス / 代謝、内分泌学

受賞

  • 2016年11月 公益財団法人MSD生命科学財団, 第5回万有医学奨励賞, 2型糖尿病候補遺伝子Kcnq1遺伝子領域による膵β細胞量調節機構の解明

    淺原俊一郎

    出版社・新聞社・財団等の賞

  • 2013年10月 AASD2013, JADEC International Research promotion Award, Paternal allelic mutation at the Kcnq1 locus reduces pancreatic beta-cell mass via epigenetic modification of Cdkn1c

    淺原 俊一郎

  • 2012年02月 日本糖尿病・肥満動物学会, 第26回日本糖尿病・肥満動物学会年次学術集会若手研究奨励賞, 2型糖尿病候補遺伝子Kcnq1遺伝子領域が膵細胞に及ぼす影響の解析

    淺原俊一郎

    国内学会・会議・シンポジウム等の賞

  • 2010年12月 分子糖尿病学研究会, 第22回分子糖尿病学シンポジウム研究奨励賞, 2型糖尿病候補遺伝子Kcnq1の膵β細胞に及ぼす役割の検討

    淺原俊一郎

    その他の賞

  • 2008年07月 日本臨床分子医学会, 第45回日本臨床分子医学会学術集会学術奨励賞, 膵β細胞における低分子量GタンパクRac1の機能解析

    淺原俊一郎

    国内学会・会議・シンポジウム等の賞

論文

  • Shun-Ichiro Asahara, Hiroyuki Inoue, Yoshiaki Kido

    The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic β-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on "gene-environment interactions" in the development of a reduced pancreatic β-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic β-cells, ultimately resulting in the development of pancreatic β-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic β-cell failure as revealed by previous reports and data from experiments.

    2022年01月, Diabetes & metabolism journal, 46 (1), 38 - 48, 英語, 国際誌

    研究論文(学術雑誌)

  • Takehito Asakawa, Michio Onizawa, Chikako Saito, Rie Hikichi, Daiki Yamada, Ai Minamidate, Tomoaki Mochimaru, Shun-Ichiro Asahara, Yoshiaki Kido, Shigeru Oshima, Takashi Nagaishi, Kiichiro Tsuchiya, Hiromasa Ohira, Ryuichi Okamoto, Mamoru Watanabe

    BACKGROUND: L-amino acids are the predominant forms of organic molecules on the planet, but recent studies have revealed that various foods contain D-amino acids, the enantiomers of L-amino acids. Though diet plays important roles in both the development and progression of inflammatory bowel disease (IBD), to our best knowledge, there has been no report on any potential interactions between D-amino acids and IBD. In this report, we aim to assess the effects of D-serine in a murine model of IBD. MATERIALS AND METHODS: To induce chronic colitis, naïve CD4 T cells (CD4+ CD62+ CD44low) from wild-type mice were adoptively transferred into Rag2-/- mice, after or before the mice were orally administered with D-serine. In vitro proliferation assays were performed to assess naïve CD4 T cell activation under the Th-skewing conditions in the presence of D-serine. RESULTS: Mice treated with D-serine prior to the induction of colitis exhibited a reduction in T-cell infiltration into the lamina propria and colonic inflammation that were not seen in mice fed with water alone or L-serine. Moreover, D-serine suppressed the progression of chronic colitis when administered after the disease induction. Under in vitro conditions, D-serine suppressed the proliferation of activated CD4 T cells and limited their ability to differentiate to Th1 and Th17 cells. CONCLUSION: Our results suggest that D-serine not only can prevent, but also has efficacious effects as a treatment for IBD.

    2021年08月, Journal of gastroenterology, 56 (8), 732 - 745, 英語, 国内誌

    研究論文(学術雑誌)

  • Guirong Han, Harumi Takahashi, Naoya Murao, Ghupurjan Gheni, Norihide Yokoi, Yoshiyuki Hamamoto, Shun-Ichiro Asahara, Yutaka Seino, Yoshiaki Kido, Susumu Seino

    AIMS/INTRODUCTION: Glutamine is the most abundant amino acid in the circulation. In this study, we investigated cell signaling in the amplification of insulin secretion by glutamine. MATERIALS AND METHODS: Clonal pancreatic β-cells MIN6-K8, wild-type B6 mouse islets, glutamate dehydrogenase (GDH) knockout clonal β-cells (Glud1KOβCL), and glutamate-oxaloacetate transaminase 1 (GOT1) knockout clonal β-cells (Got1KOβCL) were studied. Insulin secretion from these cells and islets was examined under various conditions, and intracellular glutamine metabolism was assessed by metabolic flux analysis. Intracellular Ca2+ concentration ([Ca2+ ]i ) was also measured. RESULTS: Glutamine dose-dependently amplified insulin secretion in the presence of high glucose in both MIN6-K8 cells and Glud1KOβCL. Inhibition of glutaminases, the enzymes that convert glutamine to glutamate, dramatically reduced the glutamine-amplifying effect on insulin secretion. A substantial amount of glutamate was produced from glutamine through direct conversion by glutaminases. Glutamine also increased [Ca2+ ]i at high glucose, which was abolished by inhibition of glutaminases. Glutamic acid dimethylester (dm-Glu), a membrane permeable glutamate precursor that is converted to glutamate in cells, increased [Ca2+ ]i as well as induced insulin secretion at high glucose. These effects of glutamine and dm-Glu were dependent on calcium influx. Glutamine also induced insulin secretion in clonal β-cells MIN6-m14, which otherwise exhibit no insulin secretory response to glucose. CONCLUSIONS: Glutamate converted from glutamine is an essential mediator that enhances calcium signaling in the glutamine-amplifying effect on insulin secretion. Our data also suggest that glutamine exerts a permissive effect on glucose-induced insulin secretion.

    2021年01月08日, Journal of diabetes investigation, 英語, 国内誌

    研究論文(学術雑誌)

  • Hiroyuki Inoue, Shun-ichiro Asahara, Yumiko Sugiura, Yukina Kawada, Asuka Imai, Chisako Hara, Ayumi Kanno, Maki Kimura-Koyanagi, Yoshiaki Kido

    Elsevier BV, 2020年11月, Biochemical and Biophysical Research Communications

    研究論文(学術雑誌)

  • Ayumi Kanno, Shun-Ichiro Asahara, Ayuko Furubayashi, Katsuhisa Masuda, Risa Yoshitomi, Emi Suzuki, Tomoko Takai, Maki Kimura-Koyanagi, Tomokazu Matsuda, Alberto Bartolome, Yushi Hirota, Norihide Yokoi, Yuka Inaba, Hiroshi Inoue, Michihiro Matsumoto, Kenichi Inoue, Takaya Abe, Fan-Yan Wei, Kazuhito Tomizawa, Wataru Ogawa, Susumu Seino, Masato Kasuga, Yoshiaki Kido

    EIF2AK4, which encodes the amino acid deficiency-sensing protein GCN2, has been implicated as a susceptibility gene for type 2 diabetes in the Japanese population. However, the mechanism by which GCN2 affects glucose homeostasis is unclear. Here, we show that insulin secretion is reduced in individuals harboring the risk allele of EIF2AK4 and that maintenance of GCN2-deficient mice on a high-fat diet results in a loss of pancreatic β cell mass. Our data suggest that GCN2 senses amino acid deficiency in β cells and limits signaling by mechanistic target of rapamycin complex 1 to prevent β cell failure during the consumption of a high-fat diet.

    2020年05月07日, JCI insight, 5 (9), 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • CK2活性化は膵β細胞において小胞体ストレスを改善する

    高井 智子, 松田 友和, 清家 雅子, 淺原 俊一郎, 木村 真希, 生城 浩子, 矢野 貴人, 小林 憲太, 小川 渉, 木戸 良明

    日本臨床分子医学会, 2020年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 57回, 76 - 76, 日本語

  • Atsuko Katsuyama, Sentaro Kusuhara, Shun-Ichiro Asahara, Shun-Ichiro Nakai, Sotaro Mori, Wataru Matsumiya, Akiko Miki, Takuji Kurimoto, Hisanori Imai, Yoshiaki Kido, Wataru Ogawa, Makoto Nakamura

    OBJECTIVE: To evaluate the usefulness of en face slab optical coherence tomography (OCT) imaging for monitoring diabetic retinal neurodegeneration with supporting animal experimental data. RESEARCH DESIGN AND METHODS: We retrospectively examined 72 diabetic eyes over 3 years using Cirrus-HD OCT. Two-dimensional en face slab OCT images of the innermost retina were reconstructed and graded according to the ratio of dark area to total area, and relative red, green, and blue color area ratios were calculated and used as indexes for each en face slab OCT image. Values from en face OCT images were used for statistical analyses. To obtain insight into the pathogenesis of diabetic retinal neurodegeneration, we used the InsPr-Cre;Pdk1flox/flox diabetic mouse model. RESULTS: Both OCT grade and relative red color area ratio significantly increased with the advancing stage of diabetic retinopathy (p=0.018 and 0.006, respectively). After a mean follow-up period of 4.6 years, the trend was unchanged in the analyses of 42 untreated eyes (p<0.001 and 0.001, respectively). Visual acuity showed a weak but significant negative correlation with the red color ratio on en face slab OCT images, but central retinal thickness did not exhibit a clinically meaningful correlation with values obtained from en face slab OCT images. Immunohistochemical analyses of InsPr-Cre;Pdk1flox/flox diabetic mice demonstrated the loss of ganglion axon bundles and thinning of laminin without apparent retinal vascular change at the age of 20 weeks. CONCLUSIONS: En face slab OCT imaging would be a novel useful modality for the assessment of diabetic retinal neurodegeneration as it could detect subtle optical changes occurring in the innermost retina in diabetic eyes. Our animal experimental data suggest that dark areas observed on en face slab OCT images might be the impairment of the extracellular matrix as well as neurons.

    2020年03月, BMJ open diabetes research & care, 8 (1), 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Hiroyuki Inoue, Mayumi Saito, Kumiko Kouchi, Shun-Ichiro Asahara, Fumihiko Nakamura, Yoshiaki Kido

    AIMS/INTRODUCTION: Mean platelet volume (MPV) is a widely used biological marker of platelet function and activity. Increased MPV is associated with accelerated thrombopoiesis and an elevated risk of cardiovascular disease. However, it is not known whether higher MPV is related to the pathogenesis of type 2 diabetes and diabetic macrovascular complications in Japanese patients. Therefore, we analyzed MPV and its correlation with atherosclerosis in Japanese patients with type 2 diabetes and those who had prediabetes. MATERIALS AND METHODS: We divided the patients into three groups: normoglycemic patients (n = 56), prediabetes patients (n = 44) and type 2 diabetes patients group, (n = 115). We measured platelet parameters and evaluated arterial stiffness in the three groups. RESULTS: Significantly higher MPV was found in the type 2 diabetes mellitus and prediabetes patients compared with normoglycemic patients. MPV was significantly correlated with fasting blood glucose and glycated hemoglobin levels. Multiple linear regression analysis showed that MPV was positively correlated with HbA1c, even after adjustment for confounding factors. In the evaluation of arterial stiffness by measuring the cardio-ankle vascular index and maximum intima-media thickness, MPV showed a positive correlation with these parameters. CONCLUSIONS: These findings suggest that MPV was significantly increased in the early stage of type 2 diabetes. We showed positive correlations between MPV and HbA1c levels, and between MPV and arterial stiffness in Japanese patients with type 2 diabetes.

    2019年12月12日, Journal of diabetes investigation, 英語, 国内誌

    [査読有り]

  • 造血幹細胞移植10年後に部分性脂肪萎縮症を発症したと考えられた1例

    淺原 俊一郎, 穂積 かおり, 廣田 勇士, 山本 雅昭, 福岡 秀規, 小川 渉

    (一社)日本肥満学会, 2019年10月, 肥満研究, 25 (Suppl.), 312 - 312, 日本語

    [査読有り]

  • Kanno A, Asahara S, Kawamura M, Suzuki E, Takai T, Kimura-Koyanagi M, Matsuda T, Okada Y, Ogawa W, KIDO YOSHIAKI

    AIMS/INTRODUCTION: The preservation of pancreatic β-cell mass is an essential factor in the onset and development of type 2 diabetes mellitus. Recently, sodium-glucose cotransporter 2 inhibitors have been launched as antihyperglycemic agents, and their organ-protective effects are attracting attention. They are also reported to have favorable effects on the preservation of pancreatic β-cell mass, but the appropriate timing for the administration of sodium-glucose cotransporter 2 inhibitors is obscure. MATERIALS AND METHODS: In the present study, we administered a sodium-glucose cotransporter 2 inhibitor, dapagliflozin, to an animal model of type 2 diabetes mellitus, db/db mice, and investigated the adequate timing and duration for its administration. We also carried out microarray analysis using pancreatic islets from db/db mice. RESULTS: We found that dapagliflozin preserved pancreatic β-cell mass depending on the duration of administration and markedly improved blood glucose levels. If the duration was the same, the earlier administration of dapagliflozin was more effective in preserving pancreatic β-cell mass, increasing serum insulin levels and improving blood glucose levels. From microarray analysis, we discovered that the expression of Agr2, Tff2 and Gkn3 was significantly upregulated after the early administration of dapagliflozin. This upregulated gene expression might provide a legacy effect for the preservation of pancreatic β-cell mass. CONCLUSIONS: We expect that the early administration of dapagliflozin would provide a long-lasting effect in preserving pancreatic β-cell mass.

    2019年05月, J. Diab. Invest., 10 (3), 577 - 590, 英語, 国内誌

    [査読有り]

    研究論文(学術雑誌)

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割

    高井 智子, 松田 友和, 井上 佳歩, 淺原 俊一郎, 神野 歩, 木村 真希, 小川 渉, 木戸 良明

    日本臨床分子医学会, 2019年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 56回, 65 - 65, 日本語

  • 膵β細胞特異的TSC2ノックアウトマウスにおける膵β細胞不全発症機序の解明

    伊東 春香, 淺原 俊一郎, 原 千佐子, 木村 真希, 神野 歩, 高井 智子, 木戸 良明

    (一社)日本糖尿病学会, 2019年04月, 糖尿病, 62 (Suppl.1), S - 257, 日本語

  • 2型糖尿病の病態把握におけるMPV(平均血小板容積)の有用性に関する検討

    井上 裕行, 斉藤 真裕美, 胡内 久美子, 淺原 俊一郎, 木戸 良明, 中村 文彦

    (一社)日本糖尿病学会, 2019年04月, 糖尿病, 62 (Suppl.1), S - 112, 日本語

  • Yano H, Sakai M, Matsukawa T, Yagi T, Naganuma T, Mitsushima M, Iida S, Inaba Y, Inoue H, Unoki-Kubota H, Kaburagi Y, Asahara SI, Kido Y, Minami S, Kasuga M, Matsumoto M

    Glucagon-mediated gene transcription in the liver is critical for maintaining glucose homeostasis. Promoting the induction of gluconeogenic genes and blocking that of insulin receptor substrate (Irs)2 in hepatocytes contributes to the pathogenesis of type 2 diabetes. However, the molecular mechanism by which glucagon signalling regulates hepatocyte metabolism is not fully understood. We previously showed that a fasting-inducible signalling module consisting of general control non-repressed protein 5, co-regulator cAMP response element-binding protein binding protein/p300-interacting transactivator with Glu/Asp-rich carboxy-terminal domain 2, and protein kinase A is required for glucagon-induced transcription of gluconeogenic genes. The present study aimed to identify the downstream effectors of this module in hepatocytes by examining glucagon-induced potential target genes. One of these genes was prolyl hydroxylase domain (PHD)3, which suppressed stress signalling through inhibition of the IκB kinase-nuclear factor-κB pathway in a proline hydroxylase-independent manner to maintain insulin signalling. PHD3 was also required for peroxisome proliferator-activated receptor γ coactivator 1α-induced gluconeogenesis, which was dependent on proline hydroxylase activity, suggesting that PHD3 regulates metabolism in response to glucagon as well as insulin. These findings demonstrate that glucagon-inducible PHD3 regulates glucose metabolism by suppressing stress signalling and optimising gluconeogenesis and insulin signalling in hepatocytes.

    2018年09月, Sci Rep, 8 (1), 14290 - 14290, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Docosahexaenoic Acid Reduces Palmitic Acid-Induced Endoplasmic Reticulum Stress in Pancreatic Β Cells

    Suzuki E, Matsuda T, Kawamoto T, Takahashi H, Mieda Y, Matsuura Y, Takai T, Kanno A, Koyanagi-Kimura M, Asahara SI, Inoue H, Ogawa W, Kido Y

    Endoplasmic reticulum (ER) stress leads to peripheral insulin resistance and the progression of pancreatic beta cell failure in type 2 diabetes. Although ER stress plays an important role in the pathogenesis of diabetes, it is indispensable for cellular activity. Therefore, when assessing the pathological significance of ER stress, it is important to monitor and quantify ER stress levels. Here, we have established a novel system to monitor ER stress levels quickly and sensitively, and using this method, we have clarified the effect of differences in glucose concentration and various fatty acids on the ER of pancreatic β cells. First, we developed a cell system that secretes Gaussia luciferase in culture medium depending on the activation of the GRP78 promoter. This system could sensitively monitor ER stress levels that could not be detected with real-time RT-PCR and immunoblotting. This system revealed that hyperglycemia does not induce unfolded protein response (UPR) in a short period of time in MIN6 cells, a mouse pancreatic β cell line. Physiological concentrations of palmitic acid, a saturated fatty acid, induced ER stress quickly, while physiological concentrations of oleic acid, an unsaturated fatty acid, did not. Docosahexaenoic acid, an n-3 unsaturated fatty acid, inhibited palmitic acid-induced ER stress. In this study, we have established a system that can sensitively detect ER stress levels of living cells in a short period of time. This system can be used to monitor the state of the ER in living cells and lead to the investigation of the significance of physiological or pathological ER stress levels.

    2018年09月, Kobe J Med Sci, 64 (2), E43 - E55, 英語, 国内誌

    [査読有り]

    研究論文(大学,研究機関等紀要)

  • 古林 鮎子, 神野 歩, 淺原 俊一郎, 松田 友和, 木村 真希, 木戸 良明

    (一社)日本内分泌学会, 2018年04月, 日本内分泌学会雑誌, 94 (1), 323 - 323, 日本語

  • 2型糖尿病に対する新規分子標的治療薬の確立

    松田 友和, 高井 智子, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    (一社)日本糖尿病学会, 2018年04月, 糖尿病, 61 (Suppl.1), S - 133, 日本語

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割

    高井 智子, 松田 友和, 井上 佳歩, 鈴木 江美, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    (一社)日本糖尿病学会, 2018年04月, 糖尿病, 61 (Suppl.1), S - 261, 日本語

  • ヒトiPS細胞を用いた膵内分泌細胞への分化誘導

    山田 瑞姫, 淺原 俊一郎, 下野 名奈子, 原 瑞季, 松田 友和, 高井 智子, 鈴木 江美, 木村 真希, 神野 歩, 青井 貴之, 木戸 良明

    (一社)日本糖尿病学会, 2018年04月, 糖尿病, 61 (Suppl.1), S - 386, 日本語

  • Takai T, Matsuda T, Matsuura Y, Inoue K, Suzuki E, Kanno A, Kimura-Koyanagi M, Asahara S.-i, Hatano N, Ogawa T, Kido Y

    During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to pancreatic β cell failure. CCAAT/enhancer-binding protein (C/EBP) β is highly induced by ER stress and AMP-activated protein kinase (AMPK) suppression in pancreatic β cells, and its accumulation reduces pancreatic β cell mass. We investigated the phosphorylation state of C/EBPβ under these conditions. Casein kinase 2 (CK2) was found to co-localize with C/EBPβ in MIN6 cells. It phosphorylated S222 of C/EBPβ a previously unidentified phosphorylation site. We found that C/EBPβ is phosphorylated by CK2 under AMPK suppression and ER stress, which are important from the viewpoint of the worsening pathological condition of type 2 diabetes, such as decreased insulin secretion and apoptosis of pancreatic β cells.

    Elsevier B.V., 2018年02月26日, Biochem. Biophys. Res. Commun., 497 (1), 451 - 456, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Alberto Bartolome, Ana Garcia-Aguilar, Shun-Ichiro Asahara, Yoshiaki Kido, Carlos Guillen, Utpal B. Pajvani, Manuel Benito

    Mechanistic target of rapamycin complex 1 (MTORC1) is a critical negative regulator of general autophagy. We hypothesized that MTORC1 may specifically regulate autophagic clearance of damaged mitochondria. To test this, we used cells lacking tuberous sclerosis complex 2 (TSC2(-/-) cells), which show constitutive MTORC1 activation. TSC2(-/-) cells show MTORC1-dependent impaired autophagic flux after chemical uncoupling of mitochondria, increased mitochondrial-protein aging, and accumulation of p62/SQSTM1-positive mitochondria. Mitochondrial autophagy (mitophagy) was also deficient in cells lacking TSC2, associated with altered expression of PTEN-induced putative kinase 1 (PINK1) and PARK2 translocation to uncoupled mitochondria, all of which were recovered by MTORC1 inhibition or expression of constitutively active forkhead box protein O1 (FoxO1). These data prove the necessity of intact MTORC1 signaling to regulate two synergistic processes required for clearance of damaged mitochondria: (i) general autophagy initiation and (ii) PINK1/PARK2-mediated selective targeting of uncoupled mitochondria to the autophagic machinery.

    AMER SOC MICROBIOLOGY, 2017年12月, MOLECULAR AND CELLULAR BIOLOGY, 37 (23), 英語

    [査読有り]

    研究論文(学術雑誌)

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割

    井上 佳歩, 高井 智子, 松田 友和, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 木戸 良明

    生命科学系学会合同年次大会運営事務局, 2017年12月, 生命科学系学会合同年次大会, 2017年度, [1P - 1157], 日本語

  • 高脂肪食負荷GCN2欠損マウスの膵島におけるmTORC1シグナル調節機構の解明

    古林 鮎子, 神野 歩, 増田 勝久, 吉冨 理紗, 木村 真希, 松田 友和, 淺原 俊一郎, 木戸 良明

    生命科学系学会合同年次大会運営事務局, 2017年12月, 生命科学系学会合同年次大会, 2017年度, [2P - 0995], 日本語

  • ヒトiPS細胞を用いた膵内分泌細胞への分化誘導法の確立

    山田 瑞姫, 淺原 俊一郎, 下野 名奈子, 田中 孝一, 松田 友和, 木村 真希, 神野 歩, 高井 智子, 鈴木 江美, 青井 貴之, 木戸 良明

    生命科学系学会合同年次大会運営事務局, 2017年12月, 生命科学系学会合同年次大会, 2017年度, [3P - 0838], 日本語

  • Kawada Y, Asahara SI, Sugiura Y, Sato A, Furubayashi A, Kawamura M, Bartolome A, Terashi-Suzuki E, Takai T, Kanno A, Koyanagi-Kimura M, Matsuda T, Hashimoto N, Kido Y

    Recent studies demonstrated that insulin signaling plays important roles in the regulation of pancreatic beta cell mass, the reduction of which is known to be involved in the development of diabetes. However, the mechanism underlying the alteration of insulin signaling in pancreatic beta cells remains unclear. The involvement of epigenetic control in the onset of diabetes has also been reported. Thus, we analyzed the epigenetic control of insulin receptor substrate 2 (IRS2) expression in the MIN6 mouse insulinoma cell line. We found concomitant IRS2 up-regulation and enhanced insulin signaling in MIN6 cells, which resulted in an increase in cell proliferation. The H3K9 acetylation status of the Irs2 promoter was positively associated with IRS2 expression. Treatment of MIN6 cells with histone deacetylase inhibitors led to increased IRS2 expression, but this occurred in concert with low insulin signaling. We observed increased IRS2 lysine acetylation as a consequence of histone deacetylase inhibition, a modification that was coupled with a decrease in IRS2 tyrosine phosphorylation. These results suggest that insulin signaling in pancreatic beta cells is regulated by histone dea-cetylases through two novel pathways affecting IRS2: the epigenetic control of IRS2 expression by H3K9 promoter acetylation, and the regulation of IRS2 activity through protein modification. The identification of the histone deacetylase isoform(s) involved in these mechanisms would be a valuable approach for the treatment of type 2 diabetes.

    PUBLIC LIBRARY SCIENCE, 2017年09月, PloS one, 12 (9), e0184435, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割

    高井 智子, 松田 友和, 井上 佳歩, 松浦 有希, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    (一社)日本糖尿病学会, 2017年04月, 糖尿病, 60 (Suppl.1), S - 464, 日本語

  • 脂肪酸が膵β細胞の小胞体に及ぼす影響

    鈴木 江美, 松田 友和, 川本 剛士, 松浦 有希, 高井 智子, 神野 歩, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    (一社)日本糖尿病学会, 2017年04月, 糖尿病, 60 (Suppl.1), S - 464, 日本語

  • ヒトiPS細胞を用いた2型糖尿病発症機序の解明

    下野 名奈子, 淺原 俊一郎, 原 瑞季, 田中 孝一, 松田 友和, 木村 真希, 神野 歩, 高井 智子, 鈴木 江美, 青井 貴之, 木戸 良明

    (一社)日本糖尿病学会, 2017年04月, 糖尿病, 60 (Suppl.1), S - 465, 日本語

  • 2型糖尿病の病態把握におけるMPV(平均血小板容積)の有用性に関する検討

    井上 裕行, 斉藤 真裕美, 胡内 久美子, 吉村 豊, 石田 英和, 中谷 敏也, 淺原 俊一郎, 木戸 良明, 菊池 英亮

    (一社)日本糖尿病学会, 2017年04月, 糖尿病, 60 (Suppl.1), S - 141, 日本語

  • WATANABE Hitoshi, INABA Yuka, KIMURA Kumi, ASAHARA Shunichiro, KIDO Yoshiaki, MATSUMOTO Michihiro, MOTOYAMA Takayasu, TACHIBANA Nobuhiko, KANEKO Shuichi, KOHNO Mitsutaka, INOUE Hiroshi

    Background: As the prevalence of nonalcoholic fatty liver disease (NAFLD), including steatosis and nonalcoholic steatohepatitis, is increasing, novel dietary approaches are required for the prevention and treatment of NAFLD. Objective: We evaluated the potential of mung bean protein isolate (MuPI) to prevent NAFLD progression. Methods: In Expts. 1 and 2, the hepatic triglyceride (TG) concentration was compared between 8-wk-old male mice fed a high-fat diet (61% of energy from fat) containing casein, MuPI, and soy protein isolate and an MuPI-constituent amino acid mixture as a source of amino acids (18% of energy) for 4 wk. In Expt. 3, hepatic fatty acid synthase (Fasn) expression was evaluated in 8-wk-old male Fasn-promoter-reporter mice fed a casein- or MuPI-containing high-fat diet for 20 wk. In Expt. 4, hepatic fibrosis was examined in 8-wk-old male mice fed an atherogenic diet (61 % of energy from fat, containing 1.3 g cholesterol/100 g diet) containing casein or MuPI (18% of energy) as a protein source for 20 wk. Results: In the high fat-diet mice, the hepatic TG concentration in the MuPI group decreased by 66% and 47% in Expt. 1 compared with the casein group (P < 0.001) and the soy protein isolate group (P = 0.001), respectively, and decreased by 56% in Expt. 2 compared with the casein group (P = 0.011). However, there was no difference between the MuPI-constituent amino acid mixture and casein groups in Expt. 2. In Expt. 3, Fasn-promoter-reporter activity and hepatic TG concentration were lower in the MuPI group than in those fed casein (P < 0.05). In Expt. 4, in mice fed an atherogenic diet, hepatic fibrosis was not induced in the MuPI group, whereas it developed overtly in the casein group. Conclusion: MuPI potently reduced hepatic lipid accumulation in mice and may be a potential foodstuff to prevent NAFLD onset and progression.

    AMER SOC NUTRITION-ASN, 2017年01月, Journal of Nutrition, 147 (1), 52 - 60, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 神野 歩, 増田 勝久, 淺原 俊一郎, 松田 友和, 木村 真希, 廣田 勇士, 横井 伯英, 小川 渉, 清野 進, 春日 雅人, 木戸 良明

    (一社)日本内分泌学会, 2016年04月, 日本内分泌学会雑誌, 92 (1), 242 - 242, 日本語

  • 膵β細胞不全関連分子CEBP/βの安定化に対するcasein kinase 2の役割

    高井 智子, 松田 友和, 松浦 有希, 川本 剛士, 淺原 俊一郎, 木村 真希, 神野 歩, 鈴木 江美, 小川 渉, 木戸 良明

    (一社)日本糖尿病学会, 2016年04月, 糖尿病, 59 (Suppl.1), S - 158, 日本語

  • 生物発光イメージング法による生存細胞内小胞体ストレスの定量化

    鈴木 江美, 松田 友和, 川本 剛士, 松浦 有希, 高井 智子, 神野 歩, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    (一社)日本糖尿病学会, 2016年04月, 糖尿病, 59 (Suppl.1), S - 353, 日本語

  • Kumi Kimura, Mamoru Tanida, Naoto Nagata, Yuka Inaba, Hitoshi Watanabe, Mayumi Nagashimada, Tsuguhito Ota, Shun-ichiro Asahara, Yoshiaki Kido, Michihiro Matsumoto, Koji Toshinai, Masamitsu Nakazato, Toshishige Shibamoto, Shuichi Kaneko, Masato Kasuga, Hiroshi Inoue

    Central insulin action activates hepatic IL-6/STAT3 signaling, which suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear. Here, we present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via alpha-nicotinic acetylcholine receptors (alpha 7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6/STAT3 signaling by suppressing vagal activity. Indeed, central insulin-mediated hepatic IL-6/STAT3 activation and gluconeogenic gene suppression were impeded in mice with hepatic vagotomy, pharmacological cholinergic blockade, or alpha 7-nAchR deficiency. In high-fat diet-induced obese and insulin-resistant mice, control of the vagus nerve by central insulin action was disturbed, inducing a persistent increase of inflammatory cytokines. These findings suggest that dysregulation of the alpha 7-nAchR-mediated control of Kupffer cells by central insulin action may affect the pathogenesis of chronic hepatic inflammation in obesity.

    CELL PRESS, 2016年03月, CELL REPORTS, 14 (10), 2362 - 2374, 英語

    [査読有り]

    研究論文(学術雑誌)

  • C/EBPβの蛋白安定化に関与する新規リン酸化部位の同定

    松浦 有希, 松田 友和, 高井 智子, 川本 剛士, 三枝 祐介, 鈴木 江美[寺師], 淺原 俊一郎, 木村 真希[小柳], 神野 歩, 木戸 良明

    (公社)日本生化学会, 2015年12月, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [2P1230] - [2P1230], 日本語

  • 膵β細胞不全関連分子CEBP/βの安定化に対するcasein kinase βの役割

    高井 智子, 松田 友和, 川本 剛, 松浦 有希, 淺原 俊一郎, 神野 歩, 木村 真希, 鈴木 江美[寺師], 小川 渉, 木戸 良明

    (公社)日本生化学会, 2015年12月, 日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [4T特L - 08(3P1199)], 日本語

  • Asahara S, Etoh H, Inoue H, Teruyama K, Shibutani Y, Ihara Y, Kawada Y, Bartolome A, Hashimoto N, Matsuda T, Koyanagi-Kimura M, Kanno A, Hirota Y, Hosooka T, Nagashima K, Nishimura W, Inoue H, Matsumoto M, Higgins MJ, Yasuda K, Inagaki N, Seino S, Kasuga M, Kido Y

    Genetic factors are important determinants of the onset and progression of diabetes mellitus. Numerous susceptibility genes for type 2 diabetes, including potassium voltage-gated channel, KQT-like subfamily Q, member1 (KCNQ1), have been identified in humans by genome-wide analyses and other studies. Experiments with genetically modified mice have also implicated various genes in the pathogenesis of diabetes. However, the possible effects of the parent of origin for diabetes susceptibility alleles on disease onset have remained unclear. Here, we show that a mutation at the Kcnq1 locus reduces pancreatic beta-cell mass in mice by epigenetic modulation only when it is inherited from the father. The noncoding RNA KCNQ1 overlapping transcript1 (Kcnq1ot1) is expressed from the Kcnq1 locus and regulates the expression of neighboring genes on the paternal allele. We found that disruption of Kcnq1 results in reduced Kcnq1ot1 expression as well as the increased expression of cyclin-dependent kinase inhibitor 1C (Cdkn1c), an imprinted gene that encodes a cell cycle inhibitor, only when the mutation is on the paternal allele. Furthermore, histone modification at the Cdkn1c promoter region in pancreatic islets was found to contribute to this phenomenon. Our observations suggest that the Kcnq1 genomic region directly regulates pancreatic beta-cell mass and that genomic imprinting may be a determinant of the onset of diabetes mellitus.

    NATL ACAD SCIENCES, 2015年07月, Proceedings of the National Academy of Sciences of the United States of America, 112 (27), 8332 - 8337, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Matsuda T, Takahashi H, Mieda Y, Shimizu S, Kawamoto T, Matsuura Y, Takai T, Suzuki E, Kanno A, Koyanagi-Kimura M, Asahara S, Bartolome A, Yokoi N, Inoue H, Ogawa W, Seino S, Kido Y

    During the development of type 2 diabetes, endoplasmic reticulum (ER) stress leads to not only insulin resistance but also to pancreatic beta cell failure. Conversely, cell function under various stressed conditions can be restored by reducing ER stress by activating AMP-activated protein kinase (AMPK). However, the details of this mechanism are still obscure. Therefore, the current study aims to elucidate the role of AMPK activity during ER stress-associated pancreatic beta cell failure. MIN6 cells were loaded with 5-amino-1-beta-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) and metformin to assess the relationship between AMPK activity and CCAAT enhancer binding protein beta (C/EBP beta) expression levels. The effect of C/EBP beta phosphorylation on expression levels was also investigated. Vildagliptin and metformin were administered to pancreatic beta cell-specific C/EBP beta transgenic mice to investigate the relationship between C/EBP beta expression levels and AMPK activity in the pancreatic islets. When pancreatic beta cells are exposed to ER stress, the accumulation of the transcription factor C/EBP beta lowers the AMP/ATP ratio, thereby decreasing AMPK activity. In an opposite manner, incubation of MIN6 cells with AICAR or metformin activated AMPK, which suppressed C/EBP beta expression. In addition, administration of the dipeptidyl peptidase-4 inhibitor vildagliptin and metformin to pancreatic beta cell-specific C/EBP beta transgenic mice decreased C/EBP beta expression levels and enhanced pancreatic beta cell mass in proportion to the recovery of AMPK activity. Enhanced C/EBP beta expression and decreased AMPK activity act synergistically to induce ER stress-associated pancreatic beta cell failure.

    PUBLIC LIBRARY SCIENCE, 2015年06月, PloS one, 10 (6), e0130757, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 増田 勝久, 神野 歩, 淺原 俊一郎, 吉冨 理紗, 松田 友和, 木村 真希, 渋谷 由紀, 廣田 勇士, 横井 伯英, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本内分泌学会, 2015年04月, 日本内分泌学会雑誌, 91 (1), 274 - 274, 日本語

  • 淺原 俊一郎, 杉浦 佑実子, 川田 有希奈, 伊原 佑香, 原 瑞季, 木村 真希, 松田 友和, 清野 進, 小川 渉, 木戸 良明

    (一社)日本内分泌学会, 2015年04月, 日本内分泌学会雑誌, 91 (1), 318 - 318, 日本語

  • 川本 剛士, 松田 友和, 三枝 祐介, 高井 智子, 松浦 有希, 淺原 俊一郎, 木村 真希, 神野 歩, 木戸 良明

    (一社)日本内分泌学会, 2015年04月, 日本内分泌学会雑誌, 91 (1), 319 - 319, 日本語

  • 木村 真希, 森田 愛梨, 三上 智子, 神野 歩, 松田 友和, 淺原 俊一郎, 清野 進, 小川 渉, 木戸 良明

    (一社)日本内分泌学会, 2015年04月, 日本内分泌学会雑誌, 91 (1), 352 - 352, 日本語

  • 膵β細胞不全関連因子C/EBPβの発現制御機構の解明

    高井 智子, 松田 友和, 川本 剛士, 松浦 有希, 三枝 祐介, 鈴木 江美, 淺原 俊一郎, 木村 真希, 神野 歩, 木戸 良明

    (一社)日本糖尿病学会, 2015年04月, 糖尿病, 58 (Suppl.1), S - 149, 日本語

  • 膵β細胞におけるp38経路の活性化は膵島の慢性炎症を惹起することにより膵β細胞不全の病態形成に関与する

    森田 愛梨, 細岡 哲也, 竹村 侑己, 木村 真希, 鈴木 夏実, 淺原 俊一郎, 神野 歩, 松田 友和, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2015年04月, 糖尿病, 58 (Suppl.1), S - 262, 日本語

  • ヒストン脱アセチル化酵素(HDACs)による膵β細胞量調節機構の解析

    杉浦 佑実子, 淺原 俊一郎, 川田 有希奈, 佐藤 綾香, 木村 真希, 松田 友和, 木戸 良明

    (一社)日本糖尿病学会, 2015年04月, 糖尿病, 58 (Suppl.1), S - 443, 日本語

  • 膵β細胞における細胞周期調節因子p57の機能解析

    原 瑞季, 淺原 俊一郎, 伊原 佑香, 井上 裕行, 照山 杏子, 松田 友和, 木村 真希, 中山 敬一, 木戸 良明

    (一社)日本糖尿病学会, 2015年04月, 糖尿病, 58 (Suppl.1), S - 263, 日本語

  • Ayumi Kanno, Shun-ichiro Asahara, Katsuhisa Masuda, Tomokazu Matsuda, Maki Kimura-Koyanagi, Susumu Seino, Wataru Ogawa, Yoshiaki Kido

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic beta-cells after high fat load, such as increased pancreatic beta-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic beta-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic beta-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic beta-cells. (C) 2015 Elsevier Inc. All rights reserved.

    ACADEMIC PRESS INC ELSEVIER SCIENCE, 2015年03月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 458 (3), 681 - 686, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Bartolomé A, Kimura-Koyanagi M, Asahara S, Guillén C, Inoue H, Teruyama K, Shimizu S, Kanno A, García-Aguilar A, Koike M, Uchiyama Y, Benito M, Noda T, Kido Y

    Hyperactivation of the mammalian target of rapamycin complex 1 (mTORC1) in -cells is usually found as a consequence of increased metabolic load. Although it plays an essential role in -cell compensatory mechanisms, mTORC1 negatively regulates autophagy. Using a mouse model with -cell-specific deletion of Tsc2 (Tsc2(-/-)) and, consequently, mTORC1 hyperactivation, we focused on the role that chronic mTORC1 hyperactivation might have on -cell failure. mTORC1 hyperactivation drove an early increase in -cell mass that later declined, triggering hyperglycemia. Apoptosis and endoplasmic reticulum stress markers were found in islets of older Tsc2(-/-) mice as well as accumulation of p62/SQSTM1 and an impaired autophagic response. Mitochondrial mass was increased in -cells of Tsc2(-/-) mice, but mitophagy was also impaired under these circumstances. We provide evidence of -cell autophagy impairment as a link between mTORC1 hyperactivation and mitochondrial dysfunction that probably contributes to -cell failure.

    AMER DIABETES ASSOC, 2014年09月, Diabetes, 63 (9), 2996 - 3008, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 神野 歩, 吉冨 理紗, 増田 勝久, 淺原 俊一郎, 松田 友和, 木村 真希, 澁谷 由紀, 廣田 勇士, 横井 伯英, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本内分泌学会, 2014年04月, 日本内分泌学会雑誌, 90 (1), 252 - 252, 日本語

  • 2型糖尿病感受性遺伝子GCN2は膵β細胞量の調節に関与する

    増田 勝久, 神野 歩, 吉冨 理紗, 淺原 俊一郎, 松田 友和, 木村 真希, 渋谷 由紀, 廣田 勇士, 横井 伯英, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2014年04月, 糖尿病, 57 (Suppl.1), S - 141, 日本語

  • AMPK活性依存的なC/EBPβの発現調節による膵β細胞量制御機構

    三枝 祐介, 松田 友和, 高橋 宏昌, 鈴木 江美, 川本 剛士, 淺原 俊一郎, 木村 真希, 神野 歩, 木戸 良明

    (一社)日本糖尿病学会, 2014年04月, 糖尿病, 57 (Suppl.1), S - 263, 日本語

  • 2型糖尿病感受性遺伝子GCN2は膵β細胞量の調節に関与する

    神野 歩, 吉冨 理紗, 増田 勝久, 淺原 俊一郎, 松田 友和, 木村 真希, 渋谷 由紀, 廣田 勇士, 横井 伯英, 春日 雅人, 清野 進, 木戸 良明

    日本臨床分子医学会, 2014年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 51回, 78 - 78, 日本語

  • 淺原 俊一郎, 照山 杏子, 井上 裕行, 伊原 佑香, 江藤 博昭, 川田 有希奈, 松田 友和, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本内分泌学会, 2014年04月, 日本内分泌学会雑誌, 90 (1), 267 - 267, 日本語

  • 膵β細胞のKcnq1遺伝子領域におけるエピジェネティクス制御機構の解析

    伊原 佑香, 淺原 俊一郎, 照山 杏子, 井上 裕行, 江藤 博昭, 木村 真希, 松田 友和, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2014年04月, 糖尿病, 57 (Suppl.1), S - 142, 日本語

  • Yuri Yoshida, Megumi Fuchita, Maki Kimura-Koyanagi, Ayumi Kanno, Tomokazu Matsuda, Shun-ichiro Asahara, Naoko Hashimoto, Takayuki Isagawa, Wataru Ogawa, Hiroyuki Aburatani, Tetsuo Noda, Susumu Seino, Masato Kasuga, Yoshiaki Kido

    Children born with low birth weight have a high risk of developing type 2 diabetes mellitus later in life. In this study, we developed a mouse model for low birth weight induced by maternal caloric restriction and investigated its effects on pancreatic β-cells. At birth, the pancreatic β-cell mass in the restricted diet group (RG) offspring was significantly lower than in the control group (CG) offspring. At 8 weeks of age, the pancreatic β-cell mass was greater in the RG offspring than in the CG offspring. RG offspring showed upregulated expression of insulin receptor substrate 2 in islets at 10 weeks of age. Moreover, the activity of insulin signaling molecules in the pancreatic β-cell mass was increased during the period of catch-up growth during the early stage of life. To investigate the effect of insulin signaling on the regulation of pancreatic β-cell mass, we generated β-cell-specific 3-phosphoinositide-dependent protein kinase 1 (PDK1) heterozygous knockout (βPDK1+/-) mice. We detected delayed catch-up growth in the β-cell mass of βPDK1+/- mice that were undernourished as fetuses. Moreover, the insulin signaling pathway was impaired in the islets of βPDK1+/- mice exposed to fetal undernutrition. These findings indicate that fetal undernutrition affects the regulation of pancreatic β-cell mass through altered insulin signaling. © 2013 The Japan Diabetes Society.

    Springer-Verlag Tokyo, 2014年, Diabetology International, 5 (1), 43 - 52, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 川田 有希奈, 井上 裕行, 小柳 真希, 松田 友和, 淺原 俊一郎, 木戸 良明

    (一社)日本臨床検査医学会, 2013年09月, 臨床病理, 61 (補冊), 280 - 280, 日本語

  • Kumi Kimura, Yusuke Nakamura, Yuka Inaba, Michihiro Matsumoto, Yoshiaki Kido, Shun-ichiro Asahara, Tomokazu Matsuda, Hiroshi Watanabe, Akifumi Maeda, Fuyuhiko Inagaki, Chisato Mukai, Kiyoshi Takeda, Shizuo Akira, Tsuguhito Ota, Hajime Nakabayashi, Shuichi Kaneko, Masato Kasuga, Hiroshi Inoue

    Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H-1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine HI receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

    AMER DIABETES ASSOC, 2013年07月, DIABETES, 62 (7), 2266 - 2277, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Constitutive activation of Rac1 in pancreatic β cells facilitates F-actin depolymerization but exerts no influence on the increase of pancreatic β cell mass and facilitation of insulin secretion.

    Shibutani Y, Asahara S, Teruyama K, Inoue H, Matsuda T, Seino S, Kido Y

    Insulin secretion from pancreatic β cells has an important role in the onset of type 2 diabetes. Insulin secretion from pancreatic β cells is regulated by pancreatic β cell mass and their insulin secretory function. By using pancreatic β cell-specific Rac1-knockout mice, we recently showed that Rac1 deletion, even with no reduction in pancreatic β cell mass, inhibits F-actin depolymerization, which causes insulin secretion to decline. However, the effect of Rac1 deficiency on the growth and apoptosis of pancreatic β cells was not clarified. Further, the effect of constitutive Rac1 activation on the secretion of insulin from pancreatic β cells has not been studied. Here, we used pancreatic islets isolated from pancreatic β cell-specific Rac1-knockout mice to evaluate the growth and apoptosis of pancreatic β cells. We found that Rac1 deficiency does not influence the growth or apoptosis of pancreatic β cells. Further, when a constitutively activated form of Rac1 (G12V) is expressed, F-actin depolymerization was increased in the pancreatic β cell lines, which had no effect on pancreatic β cell growth or glucose-stimulated insulin secretion. These findings indicate that excessive Rac1 expression or activation in pancreatic β cells facilitates F-actin depolymerization, but has no effect on insulin secretion.

    2013年05月08日, The Kobe journal of medical sciences, 59 (3), E72-80 - 80, 英語, 国内誌

    [査読有り]

  • S. Asahara, Y. Shibutani, K. Teruyama, H. Y. Inoue, Y. Kawada, H. Etoh, T. Matsuda, M. Kimura-Koyanagi, N. Hashimoto, M. Sakahara, W. Fujimoto, H. Takahashi, S. Ueda, T. Hosooka, T. Satoh, H. Inoue, M. Matsumoto, A. Aiba, M. Kasuga, Y. Kido

    Aims/hypothesis The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. Methods Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1(-/-)) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. Results BetaRac1(-/-) mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1(-/-) mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. Conclusions/interpretation In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion.

    SPRINGER, 2013年05月, DIABETOLOGIA, 56 (5), 1088 - 1097, 英語

    [査読有り]

    研究論文(学術雑誌)

  • DPP4阻害薬MK-626が膵β細胞特異mTORC1活性亢進モデルマウスに及ぼす影響

    三上 智子, 小柳 真希, 松田 友和, 神野 歩, 淺原 俊一郎, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2013年04月, 糖尿病, 56 (Suppl.1), S - 188, 日本語

  • インスリノーマにおけるインスリン分泌特性と遺伝子発現の解析

    小柳 真希, 松田 友和, 廣田 勇士, 橋本 尚子, 淺原 俊一郎, 中村 友昭, 木戸 良明, 坂口 一彦, 小川 渉, 清野 進

    (一社)日本内科学会, 2013年02月, 日本内科学会雑誌, 102 (Suppl.), 214 - 214, 日本語

  • Shimizu S, Hosooka T, Matsuda T, Asahara S, Koyanagi-Kimura M, Kanno A, Bartolome A, Etoh H, Fuchita M, Teruyama K, Takahashi H, Inoue H, Mieda Y, Hashimoto N, Seino S, Kido Y

    The development of type 2 diabetes is accompanied by a progressive decline in beta-cell mass and function. Vildagliptin, a dipeptidyl peptidase 4 inhibitor, is representative of a new class of antidiabetic agents that act through increasing the expression of glucagon-like peptide-1. The protective effect of this agent on beta cells was studied in diabetic mice. Diabetic pancreatic beta cell-specific C/EBPB transgenic (TG) mice exhibit decreased beta-cell mass associated with increased apoptosis, decreased proliferation, and aggravated endoplasmic reticulum (ER) stress. Vildagliptin was orally administered to the TG mice for a period of 24 weeks, and the protective effects of this agent on beta cells were examined, along with the potential molecular mechanism of protection. Vildagliptin ameliorated hyperglycemia in TG mice by increasing the serum concentration of insulin and decreasing the serum concentration of glucagon. This agent also markedly increased beta-cell mass, improved aggravated ER stress, and restored attenuated insulin/IGF1 signaling. A decrease in pancreatic and duodenal homeobox 1 expression was also observed in beta cells isolated from our mouse model, but this was also restored by vildagliptin treatment. The expression of C/EBPB protein, but not mRNA, was unexpectedly downregulated in vildagliptin-treated TG mice and in exenatide-treated MIN6 cells. Activation of the GLP1 pathway induced proteasome-dependent C/EBPB degradation in beta cells as the proteasome inhibitor MG132 restored the downregulation of C/EBPB protein by exenatide. Vildagliptin elicits protective effects on pancreatic beta cells, possibly through C/EBPB degradation, and has potential for preventing the progression of type 2 diabetes. Journal of Molecular Endocrinology (2012) 49, 125-135

    BIOSCIENTIFICA LTD, 2012年10月, Journal of molecular endocrinology, 49 (2), 125 - 135, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 膵β細胞特異的C/EBPβトランスジェニックマウスに対するビルダグリプチンの膵β細胞保護効果に関する検討

    松田 友和, 清水 忍, 細岡 哲也, 浅原 俊一郎, 高橋 宏昌, 木村 真希, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2012年04月, 糖尿病, 55 (Suppl.1), S - 298, 日本語

  • 2型糖尿病発症におけるeIF2αキナーゼGCN2の機能解析

    神野 歩, 吉冨 理紗, 淺原 俊一郎, 松田 友和, 木村 真希, 渋谷 由紀, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2012年04月, 糖尿病, 55 (Suppl.1), S - 298, 日本語

  • Kcnq1遺伝子領域におけるエピジェネティクス制御が膵β細胞量に及ぼす影響の解析

    照山 杏子, 淺原 俊一郎, 江藤 博昭, 井上 裕行, 松田 友和, 春日 雅人, 清野 進, 木戸 良明

    (一社)日本糖尿病学会, 2012年04月, 糖尿病, 55 (Suppl.1), S - 297, 日本語

  • Kcnq1遺伝子領域におけるエピジェネティクス制御が膵β細胞量に及ぼす影響の解析

    照山 杏子, 淺原 俊一郎, 江藤 博昭, 井上 裕行, 松田 友和, 清野 進, 春日 雅人, 木戸 良明

    日本臨床分子医学会, 2012年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 49回, 76 - 76, 日本語

  • Kumi Kimura, Tomoko Yamada, Michihiro Matsumoto, Yoshiaki Kido, Tetsuya Hosooka, Shun-ichiro Asahara, Tomokazu Matsuda, Tsuguhito Ota, Hiroshi Watanabe, Yoshimichi Sai, Kenichi Miyamoto, Shuichi Kaneko, Masato Kasuga, Hiroshi Inoue

    In the liver, signal transducer and activator of transcription 3 (STAT3) plays an important role in the suppression of gluconeogenic enzyme expression. While obesity-associated endoplasmic reticulum (ER) stress has been shown to increase hepatic gluconeogenic enzyme expression, the role of ER stress in STAT3-dependent regulation of such expression is unclear. The current study aimed to elucidate the effect of ER stress on the STAT3-dependent regulation of hepatic gluconeogenic enzyme expression. Genetically obese/diabetic db/db mice and db/db mouse-derived isolated hepatocytes were used as ER stress models. A tyrosine phosphatase inhibitor, a deacetylation inhibitor, and an acetylated mutant of STAT3 were used to examine the effect of ER stress on hepatic STAT3 action. ER stress inhibited STAT3-dependent suppression of gluconeogenic enzyme gene expression by suppressing hepatic Janus kinase (JAK)2 and STAT3 phosphorylation. A tyrosine phosphatase inhibitor restored ER stress-induced suppression of JAK2 phosphorylation but exhibited no improving effect on suppressed STAT3 phosphorylation. STAT3 acetylation is known to correlate with its phosphorylation. ER stress also decreased STAT3 acetylation. An acetylated mutant of STAT3 was resistant to ER stress-induced inhibition of STAT3-phosphorylation and STAT3-dependent suppression of hepatic gluconeogenic enzyme gene expression in vitro and in vivo. Trichostatin A, a histone deacetylase (HDAC) inhibitor, ameliorated ER stress-induced inhibition of STAT3 acetylation and phosphorylation. The current study revealed that ER stress inhibits STAT3-dependent suppression of hepatic gluconeogenic enzymes via JAK2 dephosphorylation and HDAC-dependent STAT3 deacetylation, playing an important role in the increase of hepatic glucose production in obesity and diabetes. Diabetes 61:61-73, 2012

    AMER DIABETES ASSOC, 2012年01月, DIABETES, 61 (1), 61 - 73, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 江藤 博昭, 淺原 俊一郎, 照山 杏子, 井上 裕行, 小柳 真希, 渋谷 由紀, 松田 友和, 長嶋 一昭, 西村 渉, 安田 和基, 稲垣 暢也, 清野 進, 春日 雅人, 木戸 良明

    (一社)日本肥満学会, 2011年09月, 肥満研究, 17 (Suppl.), 160 - 160, 日本語

  • Maki Koyanagi, Shun-ichiro Asahara, Tomokazu Matsuda, Naoko Hashimoto, Yutaka Shigeyama, Yuki Shibutani, Ayumi Kanno, Megumi Fuchita, Tomoko Mikami, Tetsutya Hosooka, Hiroshi Inoue, Michihiro Matsumoto, Masato Koike, Yasuo Uchiyama, Tetsuo Noda, Susumu Seino, Masato Kasuga, Yoshiaki Kido

    Aim: We previously found that chronic tuberous sclerosis protein 2 (TSC2) deletion induces activation of mammalian target of rapamycin Complex 1 (mTORC1) and leads to hypertrophy of pancreatic beta cells from pancreatic beta cell-specific TSC2 knockout (beta TSC2(-/-)) mice. The present study examines the effects of TSC2 ablation on insulin secretion from pancreatic beta cells. Methods: Isolated islets from beta TSC2(-/-) mice and TSC2 knockdown insulin 1 (INS-1) insulinoma cells treated with small interfering ribonucleic acid were used to investigate insulin secretion, ATP content and the expression of mitochondrial genes. Results: Activation of mTORC1 increased mitochondrial DNA expression, mitochondrial density and ATP production in pancreatic beta cells of beta TSC2(-/-) mice. In TSC2 knockdown INS-1 cells, mitochondrial DNA expression, mitochondrial density and ATP production were increased compared with those in control INS-1 cells, consistent with the phenotype of beta TSC2(-/-) mice. TSC2 knockdown INS-1 cells also exhibited augmented insulin secretory response to glucose. Rapamycin inhibited mitochondrial DNA expression and ATP production as well as insulin secretion in response to glucose. Thus, beta TSC2(-/-) mice exhibit hyperinsulinemia due to an increase in the number of mitochondria as well as enlargement of individual beta cells via activation of mTORC1 Conclusion: Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and enhances insulin secretion from pancreatic beta cells.

    PUBLIC LIBRARY SCIENCE, 2011年08月, PLOS ONE, 6 (8), e23238, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Tomokazu Matsuda, Yoshiaki Kido, Shun-ichiro Asahara, Tsuneyasu Kaisho, Takashi Tanaka, Naoko Hashimoto, Yutaka Shigeyama, Akihiko Takeda, Tae Inoue, Yuki Shibutani, Maki Koyanagi, Tetsuya Hosooka, Michihiro Matsumoto, Hiroshi Inoue, Tohru Uchida, Masato Koike, Yasuo Uchiyama, Shizuo Akira, Masato Kasuga

    Pancreatic beta cell failure is thought to underlie the progression from glucose intolerance to overt diabetes, and ER stress is implicated in such beta cell dysfunction. We have now shown that the transcription factor CCAAT/enhancer-binding protein beta (C/EBP beta) accumulated in the islets of diabetic animal models as a result of ER stress before the onset of hyperglycemia. Transgenic overexpression of C/EBP beta specifically in beta cells of mice reduced beta cell mass and lowered plasma insulin levels, resulting in the development of diabetes. Conversely, genetic ablation of C/EBP beta in the beta cells of mouse models of diabetes, including Akita mice, which harbor a heterozygous mutation in Ins2 (Ins2(WT/C96Y)), and leptin receptor-deficient (Lepr(-/-)) mice, resulted in an increase in beta cell mass and ameliorated hyperglycemia. The accumulation of C/EBP beta in pancreatic beta cells reduced the abundance of the molecular chaperone glucose-regulated protein of 78 kDa (GRP78) as a result of suppression of the transactivation activity of the transcription factor ATF6 alpha, thereby increasing the vulnerability of these cells to excess ER stress. Our results thus indicate that the accumulation of C/EBP beta in pancreatic beta cells contributes to beta cell failure in mice by enhancing susceptibility to ER stress.

    AMER SOC CLINICAL INVESTIGATION INC, 2010年01月, JOURNAL OF CLINICAL INVESTIGATION, 120 (1), 115 - 126, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Effect of intrauterine undernutrition during late gestation on pancreatic beta cell mass

    Tae Inoue, Yoshiaki Kido, Shun-ichiro Asahara, Tomokazu Matsuda, Yuki Shibutani, Maki Koyanagi, Masato Kasuga

    We analyzed the effect of low birth weight oil pancreatic beta cell mass. We used pregnant C57BL6J mice, and we reduced their food Supply by 30% during the late gestational period and examined the changes in the metabolism and pancreatic beta cell mass. Pancreatic beta cell mass at birth was greatly decreased in the mice of the food restriction group (RG) as compared to the mice of the control group (CG). The body weight of RG mice exhibited a "catch-up growth" pattern and became equivalent to that of CG mice 7 days after birth, and thereafter exceeded that of CG mice; however, the pancreatic beta cell mass in RG mice remained lower than that in CG mice at the age of 4 weeks. A high-fat diet significantly increased the pancreatic beta cell mass in RG mice as compared to that in CG mice at 12 weeks of age. However, RG mice fed oil high-fat diets tended to exhibit a decrease in the pancreatic beta cell mass at approximately 20 weeks of age. The plasma insulin concentrations also tended to be decreased in RG mice after 24 weeks of age as compared to those of CG mice. These results thus indicate that the growth of pancreatic beta cells is insufficient in RG mice, and pancreatic beta cell Failure can easily develop as a consequence Of insulin resistance.

    BIOMEDICAL RESEARCH PRESS LTD, 2009年12月, BIOMEDICAL RESEARCH-TOKYO, 30 (6), 325 - 330, 英語

    [査読有り]

    研究論文(学術雑誌)

  • Shun-ichiro Asahara, Tomokazu Matsuda, Yoshiaki Kido, Masato Kasuga

    Aim: To Study the changes in gene expression by pancreatic beta cells under insulin resistance conditions. Method: Ail exhaustive gene expression analysis was performed, Using isolated pancreatic islets of obese diabetic model Lepr I mice. Overexpression of cyclin D2 was induced in cells from the pancreatic beta cell line, namely, INS-1. Results: Through a gene expression analysis using islets isolated from db/db mice, we found a significant increase in the expression of ribosome-related molecules. In addition, increased expression of cyclin D2 was found at certain protein levels. As INS-1 cells were induced to overexpress cyclin D2, We found an increase in the expression of ribosome-related molecules. Concurrently, an increase in the expression of endoplasmic reticulum stress (ER stress)-related molecules was also found. Conclusion: in cases of pancreatic p cell hyperplasia associated with insulin resistance, ribosomal biogenesis is increased, and ER stress is induced. (C) 2009 Elsevier Inc. All rights reserved.

    ACADEMIC PRESS INC ELSEVIER SCIENCE, 2009年04月, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 381 (3), 367 - 371, 英語

    [査読有り]

    研究論文(学術雑誌)

  • 膵β細胞におけるmTORシグナルとミトコンドリア機能の検討

    小柳 真希, 木戸 良明, 浅原 俊一郎, 茂山 豊, 松田 友和, 竹田 章彦, 井上 妙, 渋谷 由紀, 清野 進, 春日 雅人

    日本臨床分子医学会, 2009年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 46回, 73 - 73, 日本語

  • 膵β細胞におけるmTORシグナルとミトコンドリア機能の検討

    小柳 真希, 木戸 良明, 浅原 俊一郎, 茂山 豊, 松田 友和, 竹田 章彦, 井上 妙, 渋谷 由紀, 清野 進, 春日 雅人

    (一社)日本糖尿病学会, 2009年04月, 糖尿病, 52 (Suppl.1), S - 217, 日本語

  • Yutaka Shigeyama, Toshiyuki Kobayashi, Yoshiaki Kido, Naoko Hashimoto, Shun-ichiro Asahara, Tomokazu Matsuda, Akihiko Takeda, Tae Inoue, Yuki Shibutani, Maki Koyanagi, Tohru Uchida, Maki Inoue, Okio Hino, Masato Kasuga, Tetsuo Noda

    Recent studies have demonstrated the importance of insulin or insulin-like growth factor 1 (IGF-1) for regulation of pancreatic beta-cell mass. Given the role of tuberous sclerosis complex 2 (TSC2) as an upstream molecule of mTOR (mammalian target of rapamycin), we examined the effect of TSC2 deficiency on beta-cell function. Here, we show that mice deficient in TSC2, specifically in pancreatic beta cells (beta TSC2(-/-) mice), manifest increased IGF-1-dependent phosphorylation of p70 S6 kinase and 4E-BP1 in islets as well as an initial increased islet mass attributable in large part to increases in the sizes of individual beta cells. These mice also exhibit hypoglycemia and hyperinsulinemia at young ages (4 to 28 weeks). After 40 weeks of age, however, the beta TSC2(-/-) mice develop progressive hyperglycemia and hypoinsulinemia accompanied by a reduction in islet mass due predominantly to a decrease in the number of beta cells. These results thus indicate that TSC2 regulates pancreatic beta-cell mass in a biphasic manner.

    AMER SOC MICROBIOLOGY, 2008年05月, MOLECULAR AND CELLULAR BIOLOGY, 28 (9), 2971 - 2979, 英語

    [査読有り]

    研究論文(学術雑誌)

  • N Hashimoto, Y Kido, T Uchida, SI Asahara, Y Shigeyama, T Matsuda, A Takeda, D Tsuchihashi, A Nishizawa, W Ogawa, Y Fujimoto, H Okamura, KC Arden, PL Herrera, T Noda, M Kasuga

    The total mass of islets of Langerhans is reduced in individuals with type 2 diabetes(1), possibly contributing to the pathogenesis of this condition. Although the regulation of islet mass is complex, recent studies have suggested the importance of a signaling pathway that includes the insulin or insulin-like growth factor-1 receptors, insulin receptor substrate and phosphatidylinositol ( PI) 3-kinase(2-4). 3-Phosphoinositide dependent protein kinase 1 (PDK1) is a serine-threonine kinase that mediates signaling downstream of PI 3-kinase. Here we show that mice that lack PDK1 specifically in pancreatic beta cells (beta Pdk1(-/-) mice) develop progressive hyperglycemia as a result of a loss of islet mass. The mice show reductions in islet density as well as in the number and size of beta cells. Haploinsufficiency of the gene for the transcription factor Foxo1 resulted in a marked increase in the number, but not the size, of beta cells and resulted in the restoration of glucose homeostasis in beta bPdk1(-/-) mice. These results suggest that PDK1 is important in maintenance of pancreatic beta cell mass and glucose homeostasis.

    NATURE PUBLISHING GROUP, 2006年05月, NATURE GENETICS, 38 (5), 589 - 593, 英語

    [査読有り]

    研究論文(学術雑誌)

  • G Tsuji, S Maekawa, K Saigo, Y Nobuhara, T Nakamura, S Kawano, M Koshiba, S Asahara, T Chinzei, S Kumagai

    Dermatomyositis (DM) has not yet been reported as a complication of myelodysplastic syndrome (MDS). A 50-year-old man was diagnosed as having MDS because of the presence of anemia, the appearance of immature cells in peripheral blood, and the abnormal cellular morphology. A few months later, high fever, myalgia and erythema developed. Although DM symptoms were resistant to high-dose corticosteroid administration, methotrexate (MTX) therapy improved not only the symptoms of DM but also hematologic findings related to MDS. This indicates that immunosuppressive therapy including MTX administration can be useful for patients with MDS with autoimmune symptoms. (C) 2003 Wiley-Liss, Inc.

    WILEY-LISS, 2003年11月, AMERICAN JOURNAL OF HEMATOLOGY, 74 (3), 175 - 178, 英語, 国際誌

    [査読有り]

    研究論文(学術雑誌)

  • Acute lymphoblastic leukemia accompanied by chromosomal abnormality of translocation (12;17)

    SI Asahara, K Saigo, N Hasuike, M Tamura, Y Maeda, Y Tomofuji, T Chinzei, E Tatsumi

    This report concerns a female patient with B-precursor acute lymphoblastic leukemia with concomitant expression of CD13 and CD33. A rare chromosomal abnormality, t(12;17)(p13;q21), was detected in 70% of metaphases analyzed. A new subgroup of acute leukemia is proposed, consisting of our case and 12 reported cases with similar chromosomal abnormalities. This subgroup has a poor prognosis and a high incidence of biphenotypic characteristics.

    VSP BV, 2001年, HAEMATOLOGIA, 31 (3), 209 - 213, 英語

    [査読有り]

    研究論文(学術雑誌)

MISC

  • Neuronatin and glucose-induced stress in pancreatic β-cells

    Asahara SI

    2018年12月, J Diabetes Investig, 英語

    記事・総説・解説・論説等(学術雑誌)

  • SGLT2 inhibitors and protection against pancreatic beta cell failure

    Asahara SI, Ogawa W

    2018年09月, Diabetol Int, 10 (1), 1 - 2, 英語

    [査読有り]

    記事・総説・解説・論説等(学術雑誌)

  • エピジェネティクスとアンチエイジング 7 糖尿病とエピジェネティクス

    淺原俊一郎, 木戸良明, 脇裕典, 山内敏正, 門脇孝

    2017年01月, アンチ・エイジング医学, 12 (6), 783‐790 - 790, 日本語

    [招待有り]

  • 2型糖尿病の病態把握におけるMPV(平均血小板容積)の有用性に関する検討

    井上裕行, 斉藤真裕美, 胡内久美子, 吉村豊, 石田英和, 中谷敏也, 淺原俊一郎, 木戸良明, 木戸良明, 菊池英亮

    2017年, 糖尿病(Web), 60 (Suppl)

  • GCN2, a type 2 diabetes mellitus susceptibility gene, is associated with the regulation of pancreatic beta cell mass

    K. Masuda, A. Kanno, S-I. Asahara, R. Yoshitomi, T. Matsuda, M. Kimura-Koyanagi, Y. Shibutani, N. Yokoi, M. Kasuga, S. Seino, Y. Kido

    SPRINGER, 2015年09月, DIABETOLOGIA, 58, S240 - S240, 英語

    研究発表ペーパー・要旨(国際会議)

  • GCN2, a Type 2 Diabetes Mellitus Susceptibility Gene, Is Associated with the Regulation of Pancreatic beta-Cell Mass

    Ayumi Kanno, Katsuhisa Masuda, Shun-Ichiro Asahara, Maki Kimura, Tomokazu Matsuda, Masato Kasuga, Wataru Ogawa, Susumu Seino, Yoshiaki Kido

    AMER DIABETES ASSOC, 2015年06月, DIABETES, 64, A599 - A599, 英語

    研究発表ペーパー・要旨(国際会議)

  • Reduction in Pancreatic beta-Cell Mass Caused by Enhanced Expression of Cdkn1c via Interaction between C/EBP beta and Epigenetic Control

    Shun-Ichiro Asahara, Yuka Ihara, Hiroyuki Inoue, Kyoko Teruyama, Mizuki Hara, Maki Kimura, Tomokazu Matsuda, Susumu Seino, Yoshiaki Kido

    AMER DIABETES ASSOC, 2015年06月, DIABETES, 64, A578 - A578, 英語

    研究発表ペーパー・要旨(国際会議)

  • Cross-interaction between C/EBPbeta and AMPK determines the pancreatic beta cell mass

    Y. Mieda, T. Matsuda, T. Kawamoto, E. Suzuki, S-I. Asahara, A. Kanno, M. Koyanagi, Y. Kido

    SPRINGER, 2014年09月, DIABETOLOGIA, 57, S191 - S191, 英語

    研究発表ペーパー・要旨(国際会議)

  • 膵β細胞のKcnq1遺伝子領域におけるエピジェネティクス制御機構の解析

    淺原 俊一郎, 照山 杏子, 伊原 佑香, 井上 裕行, 川田 有希奈, 江藤 博昭, 松田 友和, 春日 雅人, 清野 進, 木戸 良明

    日本臨床分子医学会, 2014年04月, 日本臨床分子医学会学術総会プログラム・抄録集, 51回, 77 - 77, 日本語

  • 膵β細胞における細胞周期調節蛋白p57の機能解析

    原瑞季, 淺原俊一郎, 伊原佑香, 井上裕行, 照山杏子, 松田友和, 木村(小柳)真希, 中山敬一, 木戸良明, 木戸良明

    2014年, 日本分子生物学会年会プログラム・要旨集(Web), 37th

  • 膵β細胞特異的C/EBPβトランスジェニックマウスに対するビルダグリプチンとメトホルミン併用による膵β細胞保護作用

    高橋宏昌, 松田友和, 三枝祐介, 清水忍, 淺原俊一郎, 小柳真希, 神野歩, 清野進, 木戸良明

    2013年, 糖尿病, 56 (Supplement 1)

  • インスリノーマにおけるインスリン分泌特性と遺伝子発現の解析

    小柳真希, 松田友和, 廣田勇士, 橋本尚子, 淺原俊一郎, 中村友昭, 木戸良明, 坂口一彦, 小川渉, 清野進

    2013年, 日本内科学会雑誌, 102

  • 2型糖尿病感受性遺伝子GCN2は膵β細胞量の調節に関与する

    神野歩, 吉冨理紗, 淺原俊一郎, 松田友和, 小柳真希, 渋谷由紀, 横井伯英, 春日雅人, 清野進, 木戸良明

    2013年, 糖尿病, 56 (Supplement 1)

  • DPP4阻害薬MK-626が膵β細胞特異的mTORC1活性亢進モデルマウスに及ぼす影響

    三上智子, 小柳真希, 松田友和, 神野歩, 淺原俊一郎, 春日雅人, 清野進, 木戸良明

    2013年, 糖尿病, 56 (Supplement 1)

  • 2型糖尿病候補遺伝子Kcnq1遺伝子領域が膵β細胞に及ぼす影響の解析

    井上裕行, 淺原俊一郎, 江藤博昭, 照山杏子, 伊原佑香, 渋谷由紀, 松田友和, 小柳真希, 神野歩, 西村渉, 長嶋一昭, 安田和基, 稲垣暢也, 清野進, 春日雅人, 木戸良明, 木戸良明

    2012年, 日本分子生物学会年会プログラム・要旨集(Web), 35th

  • 2型糖尿病候補遺伝子Kcnq1遺伝子領域が膵β細胞に及ぼす影響の解析

    淺原俊一郎, 江藤博昭, 照山杏子, 井上裕行, 渋谷由紀, 小柳真希, 松田友和, 長嶋一昭, 西村渉, 安田和基, 稲垣暢也, 清野進, 春日雅人, 木戸良明, 木戸良明

    2012年, 日本糖尿病・肥満動物学会年次学術集会プログラム・講演抄録集, 26th

  • インスリンシグナルが低出生体重モデルマウスの膵β細胞量調節に与える影響

    吉田有里, 淵田愛, 小柳真希, 淺原俊一郎, 松田友和, 井上妙, 春日雅人, 清野進, 木戸良明

    2012年, 糖尿病, 55 (Supplement 1)

  • 膵β細胞におけるmTORC1シグナルはミトコンドリア数増加を介してインスリン分泌を亢進させる

    小柳 真希, 淺原 俊一郎, 松田 友和, 茂山 豊, 渋谷 由紀, 神野 歩, 淵田 愛, 小池 正人, 内山 安男, 清野 進, 春日 雅人, 木戸 良明

    (一社)日本内分泌学会, 2011年04月, 日本内分泌学会雑誌, 87 (1), 279 - 279, 日本語

  • 2型糖尿病候補遺伝子KCNQ1の膵β細胞に及ぼす役割の検討

    江藤博昭, 淺原俊一郎, 照山杏子, 小柳真希, 渋谷由紀, 松田友和, 長嶋一昭, 西村渉, 安田和基, 清野進, 春日雅人, 木戸良明, 木戸良明

    2011年, 日本内分泌学会雑誌, 87 (1)

  • 低出生体重モデルマウスにおける膵β細胞量調節機構の検討

    吉田有里, 淵田愛, 小柳真希, 淺原俊一郎, 井上妙, 春日雅人, 清野進, 木戸良明, 木戸良明

    2011年, 日本分子生物学会年会プログラム・要旨集(Web), 34th

  • 低出生体重モデルマウスにおける膵β細胞量調節機構の検討

    吉田有里, 淵田愛, 小柳真希, 淺原俊一郎, 松田友和, 春日雅人, 清野進, 木戸良明, 木戸良明

    2011年, 肥満研究, 17 (Supplement)

  • 2型糖尿病候補遺伝子Kcnq1遺伝子領域が膵β細胞に及ぼす影響の解析

    淺原俊一郎, 江藤博昭, 照山杏子, 小柳真希, 渋谷由紀, 松田友和, 長嶋一昭, 西村渉, 安田和基, 清野進, 春日雅人, 木戸良明

    2011年, 糖尿病, 54 (Supplement 1)

  • 膵β細胞特異的C/EBPβトランスジェニックマウスを用いた膵β細胞不全に対するDPP-4阻害剤(ビルダグリプチン)の効果の検討

    清水忍, 細岡哲也, 松田友和, 淺原俊一郎, 小柳真希, 清野進, 木戸良明

    2011年, 糖尿病, 54 (Supplement 1)

  • 低出生体重モデルマウスにおける膵β細胞量調節機構の検討

    淵田愛, 吉田有里, 小柳真希, 淺原俊一郎, 松田友和, 井上妙, 春日雅人, 清野進, 木戸良明

    2011年, 糖尿病, 54 (Supplement 1)

  • 膵β細胞におけるelF2αキナーゼGCN2の機能解析

    神野歩, 吉冨理紗, 淺原俊一郎, 松田友和, 小柳真希, 渋谷由紀, 春日雅人, 清野進, 木戸良明

    2011年, 糖尿病, 54 (Supplement 1)

  • Ablation of TSC2 Enhances Mitochondrial Function Via Activation of mTORC1 in beta Cells

    Maki Koyanagi, Yoshiaki Kido, Shun-Ichiro Asahara, Yutaka Shigeyama, Tomokazu Matsuda, Yuki Shibutani, Megumi Fuchita, Tetsuo Noda, Susumu Seino, Masato Kasuga

    AMER DIABETES ASSOC, 2010年06月, DIABETES, 59, A91 - A91, 英語

    研究発表ペーパー・要旨(国際会議)

  • 膵β細胞におけるmTORシグナルとミトコンドリア機能の検討

    小柳 真希, 木戸 良明, 浅原 俊一郎, 茂山 豊, 松田 友和, 渋谷 由紀, 淵田 愛, 小池 正人, 内山 安男, 春日 雅人, 清野 進

    (一社)日本糖尿病学会, 2010年04月, 糖尿病, 53 (Suppl.1), S - 156, 日本語

  • Rac1 regulates glucose-induced insulin secretion through the modulation of cytoskeletal organization in beta cells

    Shun-ichiro Asahara, Yoshiaki Kido, Tomokazu Matsuda, Yuki Shibutani, Maki Koyanagi, Susumu Seino, Masato Kasuga

    JAPAN ENDOCRINE SOC, 2010年03月, ENDOCRINE JOURNAL, 57, S386 - S386, 英語

    研究発表ペーパー・要旨(国際会議)

  • 2型糖尿病候補遺伝子KCNQ1の膵β細胞に及ぼす役割の検討

    江藤博昭, 木戸良明, 木戸良明, 淺原俊一郎, 小柳真希, 渋谷由紀, 松田友和, 清野進, 春日雅人

    2010年, 糖尿病, 53 (Supplement 1)

  • 2型糖尿病候補遺伝子KCNQ1の膵β細胞に及ぼす役割の検討

    江藤博昭, 淺原俊一郎, 渋谷由紀, 小柳真希, 照山杏子, 荒木沙織, 清野進, 春日雅人, 木戸良明, 木戸良明

    2010年, 生化学

  • Effect of the Constitutive Activation of mTORC1 on Mitochondrial Function in Pancreatic beta Cells

    Maki Koyanagi, Yoshiaki Kido, Shun-Ichiro Asahara, Yutaka Shigeyama, Tomokazu Matsuda, Akihiko Takeda, Tae Inoue, Yuki Shibutani, Tohru Uchida, Susumu Seino, Masato Kasuga

    AMER DIABETES ASSOC, 2009年06月, DIABETES, 58, A2 - A2, 英語

    研究発表ペーパー・要旨(国際会議)

  • 膵β細胞における低分子量GタンパクRac1の機能解析

    淺原俊一郎, 木戸良明, 橋本尚子, 茂山豊, 松田友和, 竹田章彦, 井上妙, 渋谷由紀, 小柳真希, 内田亨, 春日雅人

    2009年, 日本内分泌学会雑誌, 85 (1)

  • 2型糖尿病候補遺伝子KCNQ1の膵β細胞に及ぼす役割の検討

    渋谷由紀, 木戸良明, 淺原俊一郎, 松田友和, 竹田章彦, 井上妙, 小柳真希, 長嶋一昭, 清野進, 春日雅人

    2009年, 糖尿病, 52 (Supplement 1)

  • Rac1 regulates glucose-induced insulin secretion through modulation of cytoskeletal organization in beta cells

    Shun-Ichiro Asahara, Yoshiaki Kido, Yutaka Shigeyama, Tomokazu Matsuda, Akihiko Takeda, Tae Inoue, Yuki Shibutani, Maki Koyanagi, Tohru Uchida, Masato Kasuga

    AMER DIABETES ASSOC, 2008年06月, DIABETES, 57, A55 - A55, 英語

    研究発表ペーパー・要旨(国際会議)

  • mTORシグナルによる膵β細胞数・サイズ調節機構の解明

    小柳真希, 木戸良明, 茂山豊, 中野尚子, 浅原俊一郎, 松田友和, 竹田章彦, 井上妙, 渋谷由紀, 内田亨, 野田哲生, 春日雅人

    2008年, 糖尿病, 51 (Supplement 1)

  • 膵β細胞における低分子量GタンパクRac1の機能解析

    浅原俊一郎, 木戸良明, 中野尚子, 茂山豊, 松田友和, 竹田章彦, 井上妙, 渋谷由紀, 小柳真希, 内田亨, 春日雅人

    2008年, 糖尿病, 51 (Supplement 1)

  • Accumulation of C/EBP beta induces pancreatic beta cell failure by reducing the endoplasmic reticulum function

    Tomokazu Matsuda, Yoshiaki Kido, Naoko Hashimoto, Shun-Ichiro Asahara, Yutaka Shigeyama, Akihiko Takeda, Tae Inoue, Yuki Shibutani, Tohru Uchida, Masato Kasuga

    AMER DIABETES ASSOC, 2007年06月, DIABETES, 56, A411 - A411, 英語

    研究発表ペーパー・要旨(国際会議)

  • Role of TSC2 in the regulation of pancreatic beta cell mass

    Yutaka Shigeyama, Yoshiaki Kido, Naoko Hashimoto, Shun-Ichiro Asahara, Tomokazu Matsuda, Akihiko Takeda, Tae Inoue, Yuki Shibutani, Tohru Uchida, Tetsuo Noda, Masato Kasuga

    AMER DIABETES ASSOC, 2007年06月, DIABETES, 56, A422 - A422, 英語

    研究発表ペーパー・要旨(国際会議)

講演・口頭発表等

  • 膵β細胞特異的PDK1ノックアウトマウスにおける前糖尿病状態の解析

    土屋 匠子, 淺原 俊一郎, 河村 真緒, 林田 彩花, 木戸 良明

    日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞特異的PDK1ノックアウトマウスにおける前糖尿病状態の解析

    土屋 匠子, 淺原 俊一郎, 河村 真緒, 林田 彩花, 木戸 良明

    第41回日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞特異的PDK1ノックアウトマウスにおける血糖値推移とβ細胞量の検討

    伊東 春香, 淺原 俊一郎, 原 千佐子, 木村 真希, 神野 歩, 高井 智子, 木戸 良明

    日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞特異的PDK1ノックアウトマウスにおける血糖値推移とβ細胞量の検討

    伊東 春香, 淺原 俊一郎, 原 千佐子, 木村 真希, 神野 歩, 高井 智子, 木戸 良明

    第41回日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2の役割

    井上 佳歩, 高井 智子, 松田 友和, 鈴木 江美, 神野 歩, 木村真希, 淺原俊一郎, 木戸良明

    日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2の役割

    井上 佳歩, 高井 智子, 松田 友和, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 木戸 良明

    第41回日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞のUnfolded Protein ResponseにおけるCK2の役割

    高井 智子, 松田 友和, 井上 佳歩, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 木戸 良明

    日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞のUnfolded Protein ResponseにおけるCK2の役割

    高井 智子, 松田 友和, 井上 佳歩, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 木戸 良明

    第41回日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞におけるGCN2/asparaginase/mTORC1シグナルの同定

    工藤 倫代, 神野 歩, 淺原 俊一郎, 松田 友和, 木村 真希, 木戸 良明

    日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • 膵β細胞におけるGCN2/asparaginase/mTORC1シグナルの同定

    工藤 倫代, 神野 歩, 淺原 俊一郎, 松田 友和, 木村 真希, 木戸 良明

    第41回日本分子生物学会年会, 2018年11月, 日本語, 横浜, 国内会議

    ポスター発表

  • Establishment of novel biomarkers for type 2 diabetes using T2DM model mice (2型糖尿病モデルマウスにおける早期診断のためのバイオマーカーの探索)

    河村 真緒, 淺原 俊一郎, 土屋 匠子, 林田 彩花, 木戸 良明

    日本細胞外小胞学会, 2018年08月, 日本語, 広島, 国内会議

    口頭発表(一般)

  • Establishment of novel biomarkers for type 2 diabetes using T2DM model mice (2型糖尿病モデルマウスにおける早期診断のためのバイオマーカーの探索)

    河村 真緒, 淺原 俊一郎, 土屋 匠子, 林田 彩花, 木戸 良明

    第5回日本細胞外小胞学会, 2018年08月, 日本語, 広島, 国内会議

    口頭発表(一般)

  • ヒトips細胞を用いた膵内分泌細胞への分化誘導

    山田 瑞姫, 淺原 俊一郎, 遠山 春希, 下野 名奈子, 原 瑞希, 田中 孝一, 松田 友和, 木村 真希, 神野 歩, 高井 智子, 鈴木 江美, 青井 貴之, 木戸 良明

    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

    その他

  • 2型糖尿病感受性遺伝子GCN2はSestrin2を介して膵β細胞量の調節に関与する

    古林 鮎子, 神野 歩, 淺原 俊一郎, 松田 友和, 木村 真希, 木戸 良明

    日本内分泌学会, 2018年04月, 日本語, 宮崎, 国内会議

    口頭発表(一般)

  • 2型糖尿病感受性遺伝子GCN2はSestrin2を介して膵β細胞量の調節に関与する

    古林 鮎子, 神野 歩, 淺原 俊一郎, 松田 友和, 木村 真希, 木戸 良明

    第91回日本内分泌学会学術総会, 2018年04月, 日本語, 宮崎, 国内会議

    口頭発表(一般)

  • GCN2, a type2 diabetes mellitus susceptibility gene, is associated with the regulation of pancreatic beta cell mass.

    Asahara S

    The 2nd International Joint Symposium -UW, UO, KU-, 2018年03月, 英語, International Joint Symposium -UW, UO, KU-, Honolulu, Hawaii, USA, 国際会議

    [招待有り]

    シンポジウム・ワークショップパネル(指名)

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割

    井上 佳歩, 高井 智子, 松田 友和, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 木戸 良明

    第40回日本分子生物学会年会, 2017年12月, 日本語, 神戸, 国内会議

    口頭発表(一般)

  • 高脂肪食負荷GCN2欠損マウスの膵島におけるmTORC1シグナル調節機構の解明

    古林 鮎子, 神野 歩, 増田 勝久, 吉富 理紗, 木村 真希, 松田 友和, 淺原 俊一郎, 木戸 良明

    第40回日本分子生物学会年会, 2017年12月, 日本語, 神戸, 国内会議

    口頭発表(一般)

  • ヒトiPS細胞を用いた膵内分泌細胞への分化誘導法の確立

    山田 瑞姫, 淺原 俊一郎, 下野 名奈子, 田中 孝一, 松田 友和, 木村 真希, 神野 歩, 高井 智子, 鈴木 江美, 青井 貴之, 木戸 良明

    第40回日本分子生物学会年会, 2017年12月, 日本語, 神戸, 国内会議

    ポスター発表

  • P-0503 Effect of removal of glucotoxicity by SGLT2 inhibitor dapagliflozin on the gene expression in pancreatic beta cells

    淺原 俊一郎, 大橋, 木戸 良明

    International Diabetes Federation, 2017年12月, 英語, Abu Dhabi, 国際会議

    ポスター発表

  • 2型糖尿病モデルマウスにおける新規バイオマーカーの探索

    河村 真緒, 土屋 匠子, 淺原 俊一郎, 木戸 良明

    第40回日本分子生物学会年会, 2017年12月, 日本語, 神戸, 国内会議

    口頭発表(一般)

  • Analysis of Pathogenic Mechanism by Susceptibility Genes of T2DM Using Human iPS Cells

    淺原 俊一郎, 木戸 良明

    77th Scientific Sessions of American Diabetes Association, 2017年06月, 英語, San Diego, 国際会議

    ポスター発表

  • 膵β細胞の小胞体ストレス誘導性アポトーシスにおけるCK2βの役割

    高井 智子, 松田 友和, 井上 佳歩, 松浦 有希, 鈴木 江美, 神野 歩, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    第60回日本糖尿病学会年次学術集会, 2017年05月, 日本語, 名古屋, 国内会議

    口頭発表(一般)

  • 脂肪酸が膵β細胞の小胞体に及ぼす影響

    鈴木 江美, 松田 友和, 川本 剛士, 松浦 有希, 高井 智子, 神野 歩, 木村 真希, 淺原 俊一郎, 小川 渉, 木戸 良明

    第60回日本糖尿病学会年次学術集会, 2017年05月, 日本語, 名古屋, 国内会議

    ポスター発表

  • ヒトIps細胞を用いた2型糖尿病発症機序の解明

    下野 名奈子, 淺原 俊一郎, 原 瑞季, 田中 孝一, 松田 友和, 木村 真希, 神野 歩, 高井 智子, 鈴木 江美, 青井 貴之, 木戸 良明

    第60回日本糖尿病学会年次学術集会, 2017年05月, 日本語, 名古屋, 国内会議

    ポスター発表

  • 2型糖尿病の病態把握におけるMPV(平均血小板容積)の有用性に関する検討

    井上 裕行, 斉藤 真裕美, 胡内 久美子, 吉村 豊, 石田 英和, 中谷 敏也, 淺原 俊一郎, 木戸 良明, 菊池 英亮

    第60回日本糖尿病学会年次学術集会, 2017年05月, 日本語, 名古屋, 国内会議

    口頭発表(一般)

共同研究・競争的資金等の研究課題

  • 2型糖尿病発症における膵β細胞でのmTORC1活性調節機構の解明

    淺原 俊一郎

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日

  • 淺原 俊一郎

    学術研究助成基金助成金/国際共同研究加速基金(国際共同研究強化(A)), 2019年, 研究代表者

    競争的資金

  • 楠原 仙太郎

    学術研究助成基金助成金/基盤研究(C), 2018年04月 - 2021年03月

    競争的資金

  • 淺原 俊一郎

    学術研究助成基金助成金/基盤研究(C), 2017年04月 - 2020年03月, 研究代表者

    競争的資金

  • 血糖降下薬がmTORC1調節を介して糖尿病発症抑制効果を示す可能性に関する検討

    神野 歩, 淺原 俊一郎

    日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2016年04月01日 - 2019年03月31日

    膵β細胞保護は2型糖尿病発症予防において重要な因子である。本研究では、各種薬剤がmTORC1シグナルに与える影響を検討し、膵β細胞量を維持することで糖尿病発症を予防すると期待される薬剤を同定することを目的とした。膵β細胞特異的TSC2遺伝子欠損マウス(βTSC2-/-マウス)にDPP-4阻害薬を、肥満2型糖尿病モデルマウスdb/dbマウスにSGLT2阻害薬を投与した。その結果、βTSC2-/-マウスの膵島においてDPP-4阻害薬のインスリンシグナル維持効果と、db/dbマウスに対するSGLT2阻害薬の膵β細胞量保持効果を認めた。

  • 淺原 俊一郎

    学術研究助成基金助成金/基盤研究(C), 2014年04月 - 2017年03月, 研究代表者

    競争的資金

  • 淺原 俊一郎

    科学研究費補助金/若手研究(B), 2012年04月 - 2014年03月, 研究代表者

    競争的資金