Functional coupling between proteins related to a novel triggered pathway for insulin secretion via TRPM2 in pancreatic beta-cells.

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K09396
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: KAKEI Masafumi 自治医科大学, 医学部, 客員教授 (90214270)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: インスリン分泌 / TRPM2チャネル / KATPチャネル / 膵β細胞

Outline of Final Research Achievements

It has long been believed that the KATP channel plays an important role in insulin secretion evoked by glucose elevation at interstitial space. In the present study we found TRPM2 channel is related more importantly to insulin secretion triggered by glucose as a mechanism other than the above channel. TRPM2 channel opens upon glucose metabolism but also upon GLP-1, intestinal hormone secretd after meal. These mechanisms are novel and postulated for playing major mechanism in healthy man because in these subjects glood glucose level is not increased after meal, We propose this impactful correctional hypothesis as another pathway in additon to KATP channel-dependent pathway in glucose-stimulated insulin secretion.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

従来考えられていたインスリン分泌機構はKATPチャネル遺族性の機序で、このチャネルの発見（1984年）以来信じられていた。本研究はこの機序に修正を求めるものであり、特に健常者においての修正が重要である。また、今後KATPチャネルの生理的意義はむしろ、肥満誘発の機序として注目されることと思われる。このように生理的意義におけるTRPM2チャネルの重要性と病態的意義としてのKATPチャネルの重要性が区別して議論されることとなると、新たな治療薬の開発にも結び付くこととなり、その社会的意義は大きい。