Functional elucidation of glucose sensing receptor: toward new understanding of glucose action

• Project/Area Number: 15K09375
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: Nakagawa Yuko 群馬大学, 生体調節研究所, 助教 (90422500)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: グルコース / インスリン / 膵β細胞 / カルシウム / 受容体

Outline of Final Research Achievements

Glucose is the most important factor regulating insulin secretion, and its mechanism of action is still unknown. We have revealed that various intracellular second messengers are activated within only a few seconds of glucose stimulation in pancreatic β cells. Unlike the response via metabolism, this rapid response was not suppressed even in the presence of a metabolic inhibitor and could be reproduced with non-metabolic glucose analogs. Therefore, it is conceivable that a series of quick response is "a glucose metabolism-independent response". It also revealed that some of these signal responses are via T1R3 and Calcium Sensing Receptor.

Research Products

• [Journal Article] Sucralose, an activator of the glucose-sensing receptor, increases ATP by calcium-dependent and -independent mechanisms. (2016)
  • Author(s): Li L, Ohtsu Y, Nakagawa Y, Masuda K, Kojima I.
  • Journal Title: Endocr. J, Volume: 63 Pages: 715-725
  • NAID: 130005261395
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Positive Allosteric Modulation of the Calcium-sensing Receptor by Physiological Concentrations of Glucose. (2016)
  • Author(s): Medina J, Nakagawa Y, Nagasawa M, Fernandez A, Sakaguchi K, Kitaguchi T, Kojima I.
  • Journal Title: J. Biol. Chem. Volume: 291 Pages: 291-291
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] 1.Glucose Evokes Rapid Ca2+ and Cyclic AMP Signals by Activating the Cell-Surface Glucose-Sensing Receptor in Pancreatic β-Cells. (2015)
  • Author(s): Nakagawa Y, Nagasawa M, Medina J, Kojima I.
  • Journal Title: PLos One. Volume: 10
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells. (2015)
  • Author(s): Hamano K, Nakagawa Y, Ohtsu Y, Li L, Medina J, Tanaka Y, Masuda K, Komatsu M, Kojima I.
  • Journal Title: J Endocrinol. Volume: 226 Pages: 57-57
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] グルコース感知受容体の分子実体の解明：CaSR ノックアウト細胞を用いた検討 (2017)
  • Author(s): 中川 祐子、ヨハン・メディナ、藤谷 与士夫 、小島 至
  • Organizer: 日本糖尿病学会
• [Presentation] T1R3ホモダイマーの機能解析 (2017)
  • Author(s): ヨハン・メディナ、中川 祐子、小島 至
  • Organizer: 日本糖尿病学会
• [Presentation] T1R3/CaSR へテロダイマーはグルコース感知受容体として機能する (2016)
  • Author(s): 中川 祐子
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-05-19