Research activity information

• Oct. 2024 第11回日本細胞外小胞学会学術集会, 奨励賞


• Mar. 2024 第37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


• Apr. 2023 第58回日本臨床分子医学会学術集会, 若手研究奨励賞

• High-Fat Diet-Fed Kcnq1 Mutant Mice Have Reduced Pancreatic β-Cell Mass via Gene-Environment Interaction.

  Shun-Ichiro Asahara, Hiroyuki Inoue, Yuka Ihara, Kyoko Teruyama, Asuka Imai, Chisako Hara, Mizuki Hara, Masako Seike, Aisha Yokoi, Nozomi Kido, Hirotaka Suzuki, Ayumi Kanno, Yuka Inaba, Hitoshi Watanabe, Go Shioi, Maki Kimura-Koyanagi, Michihiro Matsumoto, Hiroshi Inoue, Keiichi I Nakayama, Wataru Ogawa, Masato Kasuga, Yoshiaki Kido

  BACKGROUND: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA 'Kcnq1ot1,' which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. METHODS: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. RESULTS: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. CONCLUSION: This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

  Jul. 2025, Diabetes & metabolism journal, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• miR378a-3p in serum extracellular vesicles is associated with pancreatic beta-cell mass in diabetic states.

  Aisha Yokoi, Shun-Ichiro Asahara, Hiroyuki Inoue, Ayano Goto, Masako Seike, Nozomi Kido, Hirotaka Suzuki, Ayumi Kanno, Maki Kimura-Koyanagi, Kenichi Uto, Jun Saegusa, Yoshiaki Kido, Wataru Ogawa

  The condition in which the insulin secretory ability of pancreatic β-cells decreases in diabetes is extremely important, but there are currently no biomarkers that reflect pancreatic β-cell failure. Therefore, we conducted a search for biomarkers, using pancreatic β-cell-specific 3-Phosphoinositide-dependent protein kinase 1 (PDK1) knockout mice, which develop severe hyperglycemia due to a decrease in pancreatic β-cell mass without insulin resistance. The analysis was performed in young mice when metabolic abnormalities were not yet apparent. Comprehensive analysis of microRNAs contained in extracellular vesicles in the blood of these mice revealed that miR378a-3p levels were significantly lower in PDK1 knockout mice than in control mice. Furthermore, in other mouse models of diabetes, namely, db/db mice and streptozotocin-induced diabetic mice, there was an increase and decrease in miR378a-3p expression, respectively, in line with the number of β-cells. These results suggest that miR378a-3p contained in serum extracellular vesicles is a biomarker that reflects pancreatic β-cell mass before the onset of diabetes. It is hoped that miR378a-3p can be utilized to realize earlier diagnosis and treatment of diabetes.

  Mar. 2025, Biochemical and biophysical research communications, 750, 151367 - 151367, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The usefulness of HbA1c measurement in diabetic mouse models using various devices.

  Kohya Miyazaki, Aisha Yokoi, Hiroyuki Inoue, Hirotaka Suzuki, Nozomi Kido, Ayumi Kanno, Maki Kimura-Koyanagi, Yoshiaki Kido, Shun-Ichiro Asahara

  In most cases, the diagnosis of diabetes in animal models is based solely on blood glucose levels. While hemoglobin A1c (HbA1c) is widely used in the diagnosis of diabetes in humans, it is rarely measured in mice in diabetes research. This is thought to be because there are no established reference values for mouse HbA1c, as well as the fact that there are very few reports on the variability and reproducibility of measurements taken using different devices. In this study, we measured HbA1c levels in diabetic mouse models using different devices based on different principles, including capillary electrophoresis, high-performance liquid chromatography, and enzymatic methods, and compared the results. A positive correlation was observed between blood glucose and HbA1c levels in all measurement methods, and high reproducibility was confirmed in the measurement of HbA1c. However, HbA1c levels measured using the enzymatic method were slightly higher than those measured using the other two methods. In addition, an examination of diabetic mice given a sodium-glucose cotransporter 2 inhibitor, which is used to treat diabetes, revealed that there was a 2-week difference in the fluctuation of mouse HbA1c levels compared with the fluctuation of blood glucose levels. Based on these results, it is thought that HbA1c can be a reliable indicator in diabetic mouse models, and it is expected to make the evaluation of abnormal glucose metabolism in mice more reliable.

  Jan. 2025, Experimental animals, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Dapagliflozin administration to a mouse model of type 2 diabetes induces DNA methylation and gene expression changes in pancreatic islets.

  Aisha Yokoi, Shun-Ichiro Asahara, Hiroyuki Inoue, Masako Seike, Nozomi Kido, Hirotaka Suzuki, Ayumi Kanno, Maki Kimura-Koyanagi, Yoshiaki Kido, Wataru Ogawa

  Decreased pancreatic β-cell volume is a serious problem in patients with type 2 diabetes mellitus, and there is a need to establish appropriate treatments. Increasingly, sodium/glucose cotransporter 2 (SGLT2) inhibitors, which have a protective effect on pancreatic β-cells, are being prescribed to treat diabetes; however, the underlying mechanism is not well understood. We previously administered SGLT2 inhibitor dapagliflozin to a mouse model of type 2 diabetes and found significant changes in gene expression in the early-treated group, which led us to hypothesize that epigenetic regulation was a possible mechanism of these changes. Therefore, we performed comprehensive DNA methylation analysis by methylated DNA immunoprecipitation using isolated pancreatic islets after dapagliflozin administration to diabetic model mice. As a result, we identified 31 genes with changes in expression due to DNA methylation changes. Upon immunostaining, cystic fibrosis transmembrane conductance regulator and cadherin 24 were found to be upregulated in islets in the dapagliflozin-treated group. These molecules may contribute to the maintenance of islet morphology and insulin secretory capacity, suggesting that SGLT2 inhibitors' protective effect on pancreatic β-cells is accompanied by DNA methylation changes, and that the effect is long-term and not temporary. In future diabetes care, SGLT2 inhibitors may be expected to have positive therapeutic effects, including pancreatic β-cell protection.

  Sep. 2024, Biochemical and biophysical research communications, 725, 150254 - 150254, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• l-Asparaginase regulates mTORC1 activity via a TSC2-dependent pathway in pancreatic beta cells.

  Masako Seike, Shun-Ichiro Asahara, Hiroyuki Inoue, Michiyo Kudo, Ayumi Kanno, Aisha Yokoi, Hirotaka Suzuki, Maki Kimura-Koyanagi, Yoshiaki Kido, Wataru Ogawa

  Eif2ak4, a susceptibility gene for type 2 diabetes, encodes GCN2, a molecule activated by amino acid deficiency. Mutations or deletions in GCN2 in pancreatic β-cells increase mTORC1 activity by decreasing Sestrin2 expression in a TSC2-independent manner. In this study, we searched for molecules downstream of GCN2 that suppress mTORC1 activity in a TSC2-dependent manner. To do so, we used a pull-down assay to identify molecules that competitively inhibit the binding of the T1462 phosphorylation site of TSC2 to 14-3-3. l-asparaginase was identified. Although l-asparaginase is frequently used as an anticancer drug for acute lymphoblastic leukemia, little is known about endogenous l-asparaginase. l-Asparaginase, which is expressed downstream of GCN2, was found to bind 14-3-3 and thereby to inhibit its binding to the T1462 phosphorylation site of TSC2 and contribute to TSC2 activation and mTORC1 inactivation upon TSC2 dephosphorylation. Further investigation of the regulation of mTORC1 activity in pancreatic β-cells by l-asparaginase should help to elucidate the mechanism of diabetes and insulin secretion failure during anticancer drug use.

  Apr. 2023, Biochemical and biophysical research communications, 652, 121 - 130, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Association between diabetic nephropathy and left ventricular longitudinal myocardial function in type 1 diabetes mellitus patients with preserved ejection fraction.

  Eri Ota, Hidekazu Tanaka, Yasuhide Mochizuki, Yuki Yamauchi, Hiroaki Shiraki, Kentaro Yamashita, Ayu Shono, Makiko Suzuki, Keiko Sumimoto, Aisha Yokoi, Shin Urai, Yushi Hirota, Wataru Ogawa, Ken-Ichi Hirata

  Left ventricular (LV) longitudinal myocardial dysfunction can be observed even in type 2 diabetes mellitus (DM) (T2DM) patients with preserved LV ejection fraction (LVEF), and is considered the earliest marker of DM-related cardiac dysfunction. Furthermore, diabetic nephropathy (DN), a common complication in DM, is strongly associated with LV longitudinal myocardial function in T2DM patients, but its association with type 1 DM (T1DM) has not been fully investigated. We studied 125 asymptomatic T1DM patients with preserved LVEF, and 75 age-, gender-, LVEF-matched non-diabetic healthy controls. Two-dimensional speckle-tracking strain LV was used to assess longitudinal myocardial function as global longitudinal strain (GLS). GLS of T1DM patients was significantly lower than that of normal controls (19.7 ± 3.6% vs. 20.6 ± 1.8%, P = 0.049). GLS of T1DM patients with DN was significantly lower that of T1DM patients without DN (17.3 ± 3.7% vs. 20.2 ± 3.5%, P < 0.001), but that of T1DM patients without DN was similar compared to normal controls (20.6 ± 1.8% vs. 20.2 ± 3.5%, P = 0.37). Moreover, multiple regression analysis identified DN the independent determinant parameters for GLS of T1DM patients also correlated significantly with duration of T1DM. Impaired LV longitudinal myocardial function was observed in asymptomatic T1DM patients with preserved LVEF, and DN was associated with LV longitudinal myocardial dysfunction. These findings are clinically useful for better management of T1DM patients to prevent impending development of cardiovascular disease.

  Sep. 2022, The international journal of cardiovascular imaging, 38(9) (9), 1991 - 1998, English, International magazine

  Scientific journal

• 糖尿病状態における膵β細胞由来エクソソームの動態解明

  横井 愛紗, 淺原 俊一郎, 木村 真希, 鈴木 宏隆, 木戸 希, 藤井 智子, 井上 裕行, 木戸 良明, 小川 渉

  日本臨床分子医学会, Apr. 2025, 日本臨床分子医学会学術総会プログラム・抄録集, 60回, 49 - 49, Japanese


• 骨格筋および脂肪細胞由来エクソソームの動態に関する検討

  鈴木 宏隆, 淺原 俊一郎, 横井 愛紗, 木戸 希, 藤井 智子, 木村 真希, 木戸 良明, 小川 渉

  (一社)日本糖尿病学会, Apr. 2025, 糖尿病, 68(Suppl.) (Suppl.), S - 187, Japanese


• 膵β細胞由来エクソソームの臓器連関に関する解析

  井上裕行, 横井愛紗, 後藤綾乃, 篠塚祐奈, 藤井智子, 木戸良明, 淺原俊一郎

  2025, 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, 38th


• 膵β細胞におけるmTORC1活性化が膵島可塑性に及ぼす影響の検討

  木戸 希, 淺原 俊一郎, 清家 雅子, 木村 真希, 鈴木 宏隆, 横井 愛紗, 椎木 幾久子, 田部 勝也, 木戸 良明, 小川 渉

  (一社)日本糖尿病学会, Apr. 2024, 糖尿病, 67(Suppl.1) (Suppl.1), S - 160, Japanese


• 骨格筋由来エクソソームの動態および糖代謝に及ぼす影響の解析

  鈴木 宏隆, 淺原 俊一郎, 横井 愛紗, 木戸 希, 木村 真希, 木戸 良明, 小川 渉

  (一社)日本糖尿病学会, Apr. 2024, 糖尿病, 67(Suppl.1) (Suppl.1), S - 174, Japanese


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  横井愛紗, 淺原俊一郎, 木村真希, 木戸希, 鈴木隆弘, 木戸良明, 小川渉

  2024, 日本内分泌学会雑誌, 100(1) (1)


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  横井愛紗, 淺原俊一郎, 木村真希, 鈴木宏隆, 木戸希, 木戸良明, 小川渉

  2024, 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, 37th


• 骨格筋由来エクソソームの動態および糖代謝に及ぼす影響の解析

  鈴木宏隆, 淺原俊一郎, 横井愛紗, 木戸希, 木村真希, 木戸良明, 小川渉

  2024, 糖尿病(Web), 67(Suppl) (Suppl)


• 膵β細胞におけるmTORC1活性化が膵島可塑性に及ぼす影響の検討

  木戸希, 淺原俊一郎, 清家雅子, 木村真希, 鈴木宏隆, 横井愛紗, 椎木幾久子, 田部勝也, 木戸良明, 小川渉

  2024, 糖尿病(Web), 67(Suppl) (Suppl)


• 膵β細胞におけるmTORC1活性化は膵外分泌細胞への分化を誘導する

  清家 雅子, 淺原 俊一郎, 木村 真希, 鈴木 宏隆, 横井 愛紗, 椎木 幾久子, 田部 勝也, 木戸 良明, 小川 渉

  (一社)日本糖尿病学会, Apr. 2023, 糖尿病, 66(Suppl.1) (Suppl.1), S - 186, Japanese


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  横井愛紗, 淺原俊一郎, 木村真希, 清家雅子, 鈴木宏隆, 木戸良明, 小川渉

  2023, 糖尿病(Web), 66(Suppl) (Suppl)


• 1型糖尿病患者における心エコー図を用いた左室拡張機能の検討

  横井 愛紗, 浦井 伸, 山本 雅昭, 福岡 秀規, 岡田 裕子, 田中 秀和, 廣田 勇士, 小川 渉

  日本先進糖尿病治療研究会, Dec. 2022, 日本先進糖尿病治療研究会雑誌, 16(2) (2), 63 - 63, Japanese


• 膵β細胞におけるmTORC1恒常的活性化と膵島可塑性の関連についての検討

  清家 雅子, 淺原 俊一郎, 伊東 春香, 木村 真希, 鈴木 宏隆, 横井 愛紗, 神野 歩, 木戸 良明, 小川 渉

  (一社)日本糖尿病学会, Apr. 2022, 糖尿病, 65(Suppl.1) (Suppl.1), S - 217, Japanese


• 成人期診断22q11.2欠失症候群における内分泌異常の検討

  横井 愛紗, 福岡 秀規, 山本 雅昭, 穂積 かおり, 廣田 勇士, 小川 渉

  (一社)日本内分泌学会, Apr. 2021, 日本内分泌学会雑誌, 97(1) (1), 336 - 336, Japanese


• 成人期診断22q11.2欠失症候群における内分泌異常の特徴

  横井 愛紗, 福岡 秀規, 穂積 かおり, 山本 雅昭, 廣田 勇士, 小川 渉, 高橋 裕

  (一社)日本内分泌学会, Oct. 2019, 日本内分泌学会雑誌, 95(2) (2), 821 - 821, Japanese


• パラガングリオーマの治療で著明な血糖コントロール改善を認めた高齢糖尿病患者の1例

  貴志 豪俊, 横井 愛紗, 佐々木 百合子, 前田 ゆき, 錢林 雅子, 梶川 道子, 北村 泰明, 浅利 貞毅, 河野 洋, 寺村 一裕

  (一社)日本糖尿病学会, Apr. 2019, 糖尿病, 62(4) (4), 244 - 244, Japanese


• 細菌性髄膜炎を発症し、脳皮質下出血を合併した2型糖尿病患者の1例

  横井 愛紗, 佐々木 百合子, 貴志 豪俊, 前田 ゆき, 錢林 雅子, 梶川 道子

  (一社)日本糖尿病学会, Apr. 2019, 糖尿病, 62(4) (4), 294 - 294, Japanese


• 当院での抗PD-1抗体使用85名における内分泌関連irAEについて

  貴志 豪俊, 佐々木 百合子, 横井 愛紗, 前田 ゆき, 錢林 雅子, 梶川 道子

  (一社)日本内分泌学会, Apr. 2019, 日本内分泌学会雑誌, 95(1) (1), 384 - 384, Japanese


• 低血糖により入院加療を要した2型糖尿病患者101例の検討

  横井 愛紗, 錢林 雅子, 佐々木 百合子, 貴志 豪俊, 前田 ゆき, 梶川 道子

  (一社)日本糖尿病学会, Apr. 2019, 糖尿病, 62(Suppl.1) (Suppl.1), S - 355, Japanese


• 2型糖尿病に合併した成人発症の周期性ACTH-ADH放出症候群の1例

  横井 愛紗, 佐々木 百合子, 貴志 豪俊, 前田 ゆき, 錢林 雅子, 梶川 道子

  (一社)日本内分泌学会, Sep. 2018, 日本内分泌学会雑誌, 94(2) (2), 675 - 675, Japanese


• 2型糖尿病の治療中に1型糖尿病を発症した1例

  貴志 豪俊, 佐々木 百合子, 横井 愛紗, 前田 ゆき, 錢林 雅子, 梶川 道子

  (一社)日本糖尿病学会, Jun. 2018, 糖尿病, 61(6) (6), 423 - 423, Japanese


• 当院におけるデュラグルチド使用患者の特徴と有効性の検討

  貴志 豪俊, 錢林 雅子, 佐々木 百合子, 横井 愛紗, 前田 ゆき, 梶川 道子

  (一社)日本糖尿病学会, Apr. 2018, 糖尿病, 61(Suppl.1) (Suppl.1), S - 368, Japanese

• 研修医の医療安全意識向上に向けた当院研修開始時シミュレーション研修と診療科発信型報告体制の構築

  第58回日本医学教育学会学術大会, Aug. 2026


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  第60回日本臨床分子医学会学術集会, Apr. 2025


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  第11回日本細胞外小胞学会学術集会（JSEV2024）, Oct. 2024


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  第97回日本内分泌学会学術総会, Jun. 2024


• 糖尿病病態における膵β細胞由来エクソソームの動態および役割の解明

  第66回日本糖尿病学会年次学術集会, May 2023

• 膵β細胞由来エクソソームの膵β細胞-脳臓器連関への関与について

  横井 愛紗

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, Apr. 2026 - Mar. 2029


• 細胞外小胞内miR378a-3pの膵β細胞量バイオマーカーとしての有用性に関する検討

  横井 愛紗

  日本学術振興会, 科学研究費助成事業, 研究活動スタート支援, 神戸大学, Jul. 2025 - Mar. 2027