Analysis of the mechanism of GCN2 activation in pancreatic beta cells

• Project/Area Number: 25461352
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: Kido Yoshiaki 神戸大学, 保健学研究科, 教授 (10335440)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 膵β細胞 / アミノ酸 / 2型糖尿病

Outline of Final Research Achievements

We have previously clarified that GCN2 deficient mice displayed a reduced pancreatic beta cell mass. In this study, we aimed at elucidating the mechanism of the phenotype. As a result, GCN2 was found to regulate global translation by suppressing mTORC1 activity in beta cells when insulin translation was upregulated. This study showed that GCN2 inactivation or deficient resulted in pancreatic beta cell failure.

Research Products

• [Journal Article] Centra insulin-action activates Kupffer cells by suppressing hepatic vagal activation through nicotinic alpha 7 acetylcholine receptor. (2016)
  • Author(s): Kimura K, Tanida M, Nagata N, Inaba Y, Watanabe H, Nagashimada M, Ota T, Asahara S, Kido Y, Matsumoto M, Toshinai K, Nakazato M, Shibamoto T, Kaneko S, Kasuga M, Inoue H
  • Journal Title: Cell reports Volume: 14 Issue: 10 Pages: 2362-2374
  • DOI: 10.1016/j.celrep.2016.02.032
  • Peer Reviewed / Open Access
• [Journal Article] A case of hemiplegia with hypoglycemia possibly associated with hemodynamic change. (2015)
  • Author(s): Matsuda T, Iwasaki M, Yoshioka N, Hirota Y, Hamaguchi H, Kido Y, Sakaguchi K, Ogawa W
  • Journal Title: Diabetology International Volume: 6 Pages: 336-340
  • Peer Reviewed / Open Access
• [Journal Article] Paternal allelic mutation at the Kcnq1 locus reduces pancreatic β cell mass via epigenetic modification of Cdkn1c. (2015)
  • Author(s): 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.
  • Journal Title: Proceedings of the National Acaddemy of Scienceof the United States of America Volume: 112(27) Issue: 27 Pages: 8332-8337
  • DOI: 10.1073/pnas.1422104112
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of pancreatic β cell mass by cross-interaction between CCAAT enhancer binding protein β induced by endoplasmic reticulum stress and AMP-activated protein kinase activity. (2015)
  • Author(s): Matsuda T, Takahashi H, Mieda Y, Shimizu S, Kawamoto T, Matsuura Y, Takai T, Suzuki E, Koyanagi-Kimura M, Asahara S, Bartolome A, Yokoi N, Inoue H, Ogawa W, Seino S, Kido Y
  • Journal Title: PLoS ONE Volume: 10 Issue: 6 Pages: e0130757-e0130757
  • DOI: 10.1371/journal.pone.0130757
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets (2015)
  • Author(s): Kanno A, Asahara SI, Masuda K, Matsuda T, Kimura-Koyanagi M, Seino S, Ogawa W, Kido Y
  • Journal Title: Biochem Biophys Res Commun Volume: 458 Issue: 3 Pages: 681-686
  • DOI: 10.1016/j.bbrc.2015.02.024
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] GCN2, a Type 2 Diabetes Mellitus Susceptibility Gene, Is Associated with the Regulation of Pancreatic β-Cell Mass (2015)
  • Author(s): Kanno A, Masuda K, Asahara S, Kimura M, Matsuda T, Kasuga M, Ogawa W, Seino S, Kido Y
  • Organizer: 75th Scientific Session of American Diabetes Association
  • Place of Presentation: ボストン
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] ２型糖尿病疾患感受性遺伝子による膵β細胞量調節機構 (2015)
  • Author(s): 木戸良明
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口
  • Year and Date: 2015-05-21
  • Invited
• [Presentation] 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 (2014)
  • Author(s): 増田 勝久、神野 歩、吉冨 理紗、淺原 俊一郎、松田 友和、木村(小柳) 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
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25 – 2014-11-27
• [Presentation] 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 (2014)
  • Author(s): 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
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 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 (2014)
  • Author(s): 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
  • Organizer: 第87回日本内分泌学会学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-04-24 – 2014-04-26
• [Presentation] 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 (2014)
  • Author(s): 神野歩、吉冨理紗、増田勝久、浅原俊一郎、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
  • Organizer: 第28回日本糖尿病・肥満動物学会年次学術集会
  • Place of Presentation: 宮崎市民プラザ
• [Presentation] 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 (2013)
  • Author(s): 神野歩、吉冨理紗、浅原俊一郎、松田友和、小柳真希、澁谷由紀、横井伯英、春日雅人、清野進、木戸良明
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: ホテル日航熊本