Elucidation of the regulation of expression of receptors for incretin and PACAP in pancreatic beta cells

• Project/Area Number: 25670435
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Yokohama City University
• Principal Investigator: TERAUCHI Yasuo 横浜市立大学, 医学(系)研究科(研究院), 教授 (40359609)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: 膵β細胞 / インクレチン / PACAP / インクレチン受容体

Outline of Final Research Achievements

We investigated the effects of glucose and AMPK in the regulation of incretin receptors expression in pancreatic islets. The expression of incretin receptors in bell-shaped response to glucose; Expression of the incretin receptors in the isolated islets showed higher levels under a medium glucose concentration (11.1 mM) than that under a low glucose concentration (2.8 mM), but was suppressed under a high glucose concentration (22.2 mM). The phosphorylation of AMPK in the mouse islets was decreased by increasing glucose concentrations. Both treatment with an AMPK inhibitor and DN-AMPK expression produced a significant increase of the incretin receptors expression under a low glucose concentration. Taken together, AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration.

Research Products

• [Journal Article] Present status of clinical deployment of glucokinase activators. (2015)
  • Author(s): Nakamura A, Terauchi Y.
  • Journal Title: J Diabetes Investig Volume: ６ Pages: 124-132
  • Peer Reviewed / Open Access
• [Journal Article] β cell proliferation after a partial pancreatectomy is independent of IRS-2 in mice. (2014)
  • Author(s): Togashi Y, Shirakawa J, Orime K, Kaji M, Sakamoto E, Tajima K, Inoue H, Nakamura A, Tochino Y, Goshima Y, Shimomura I, Terauchi Y.
  • Journal Title: Ｅｎｄｏｃｒｉｎｏｌｏｇｙ Volume: 155(5) Pages: 1643-52
  • Peer Reviewed / Open Access
• [Journal Article] Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β cell functions, and β cell proliferation in male mice． (2014)
  • Author(s): Shirakawa J, Okuyama T, Yoshida E, Shimizu M, Horigome Y, Tuno T, Hayasaka M, Abe S, Fuse M, Togashi Y, Terauchi Y.
  • Journal Title: Ｅｎｄｏｃｒｉｎｏｌｏｇｙ Volume: 155(6) Pages: 2102-11
  • Peer Reviewed / Open Access
• [Journal Article] β cell proliferation after a partial pancreatectomy is independent of IRS-2 in mice. (2014)
  • Author(s): Togashi Y, Shirakawa J, Orime K, Kaji M, Sakamoto E, Tajima K, Inoue H, Nakamura A, Tochino Y, Goshima Y, Shimomura I, Terauchi Y.
  • Journal Title: Endocrinology Volume: 155 Issue: 5 Pages: 1643-52
  • DOI: 10.1210/en.2013-1796
  • Peer Reviewed
• [Journal Article] Effects of the antitumor drug OSI-906, a dual inhibitor of IGF-1 receptor and insulin receptor, on the glycemic control, β cell functions, and β cell proliferation in male mice. (2014)
  • Author(s): Shirakawa J, Okuyama T, Yoshida E, Shimizu M, Horigome Y, Tuno T, Hayasaka M, Abe S, Fuse M, Togashi Y, Terauchi Y.
  • Journal Title: Endocrinology Volume: 155
  • Peer Reviewed
• [Journal Article] AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under a low glucose concentration. (2013)
  • Author(s): Tajima K, Shirakawa J, Togashi Y, Inoue H, Sato K, Orime K, Ito Y, Kaji M, Sakamoto E, Nakamura A, Aoki K, Goshima Y, Atsumi T, Terauchi Y.
  • Journal Title: PLoS One. Volume: 8 Issue: 5 Pages: e64633-e64633
  • DOI: 10.1371/journal.pone.0064633
  • Peer Reviewed
• [Journal Article] Glucokinase activation ameliorates ER stress-induced apoptosis in pancreatic β cells. (2013)
  • Author(s): Shirakawa J, Togashi Y, Sakamoto E, Kaji M, Tajima K, Orime K, Inoue H, Kubota N, Kadowaki T, Terauchi Y.
  • Journal Title: Diabetes Volume: 62 Issue: 10 Pages: 3448-58
  • DOI: 10.2337/db13-0052
  • Peer Reviewed
• [Presentation] Different effect of short-term and long-term high-fat diet feeding on pancreatic beta cell proliferation. (2014)
  • Author(s): Kitao N, Nakamura A, Nomoto H, Miyoshi H, Terauchi Y, Atsumi T
  • Organizer: 10th IDF-WPR Congress/6th AASD Scientific Meeting,
  • Place of Presentation: Singapore, Singapore
  • Year and Date: 2014-11-20 – 2014-11-21
• [Presentation] The role of S100A8 and S100A9 in inflammatory interaction between pancreatic islets and macrophages. (2014)
  • Author(s): Inoue H, Shirakawa J, Orime K, Togashi Y, Tajima K, Terauchi Y: The role of S100A8 and S100A9 in inflammatory interaction between pancreatic islets and macrophages.
  • Organizer: 50th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] Isolation of target genes of liraglutide, a GLP-1 receptor agonist, in pancreatic islets by using nano-LC-MS/MS system. (2014)
  • Author(s): Yoshida E, Shirakawa J, Okuyama T, Kyohara M, Togashi Y, Kimura A, Hirano H, Terauchi Y
  • Organizer: 50th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2014-09-15 – 2014-09-19
• [Presentation] AMPK is involved in the regulation of incretin receptors expression in pancreatic islets under low and medium glucose concentrations. (2013)
  • Author(s): Tajima K, Shirakawa J, Togashi Y, Terauchi Y
  • Organizer: Beta Cell Workshop 2013 Kyoto
  • Place of Presentation: 国立京都国際会館（京都府京都市）
• [Presentation] Glucokinase activation ameliorates ER stress-induced apoptosis in pancreatic β cells. (2013)
  • Author(s): Shirakawa J, Terauchi Y
  • Organizer: Beta Cell Workshop 2013 Kyoto
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Invited
• [Presentation] Impact of glucokinase activation on proliferation and apoptosis of pancreatic beta cells. (2013)
  • Author(s): Terauchi Y
  • Organizer: Beta Cell Workshop 2013 Kyoto
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Invited
• [Presentation] Characterization of target genes of glucokinase activator (GKA) in pancreatic islets. (2013)
  • Author(s): Shirakawa J, Terauchi Y
  • Organizer: 73rd American Diabetes Association (ADA) meeting
  • Place of Presentation: Chicago, USA.
• [Presentation] Coordinated effects of macrophages and free fatty acids on the inflammatory gene expression in pancreatic islets. (2013)
  • Author(s): Inoue H, Shirakawa J, Orime K, Togashi Y, Terauchi Y
  • Organizer: 49th Annual Meeting of the European Association for the Study of Diabetes
  • Place of Presentation: Barcelona, Spain
• [Remarks] 横浜市立大学大学院医学研究科 分子内分泌・糖尿病内科学教室
  • URL: http://www-user.yokohama-cu.ac.jp/~nai3naib/
• [Remarks] 横浜市立大学大学院 医学研究科 分子内分泌・糖尿病内科学教室
  • URL: http://www-user.yokohama-cu.ac.jp/~nai3naib/