Elucidation of the molecular mechanism of GLP-1/glucoreceptor/KATP crosstalk in pancreatic b cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K08525
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Jichi Medical University
• Principal Investigator: Yoshida Masashi 自治医科大学, 医学部, 准教授 (50528411)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Keywords: 膵β細胞 / インスリン分泌 / TRPM2 / cADPR / ランゲルハンス等

Outline of Final Research Achievements

Although elucidating the mechanism of first phase insulin secretion in healthy individuals is directly linked to the prevention of type 2 diabetes, this has not received much attention. We have discovered a new insulin secretion pathway (Trpm2 pathway) and reported that its existence is essential for the first phase insulin secretion. This study hypothesized that impairment of the Trpm2 pathway is involved in the onset of diabetes. In this study, we discovered the mechanism of the new antidiabetic drug Imeglimin, and demonstrated that GK rats develop type 2 diabetes due to impairment of the glucose/CD38/cADPR-mediated pathway. The results of this study are significant in that they have revealed a new mechanism of diabetes onset.

Free Research Field

膵β細胞インスリン分泌

Academic Significance and Societal Importance of the Research Achievements

２型糖尿病患者は増加の一途であり、その合併症による患者の生活の質低下のみならず、医療経済的にも大きな問題となりつつある。しかしながら、多くの研究者が治療薬や治療法の開発・研究に注力しているものの、発症予防に主眼を置いた研究は殆ど無い。本研究は２型糖尿病発症初期段階で低下する第１相インスリン分泌の機序解明と、障害部位の同定、治療介入による２型糖尿病発症抑制を目的として立案した。本研究で我々は新たな２型糖尿病発症機序を見出し、新規糖尿病薬イメグリミンはその経路を介してインスリン分泌を増強することを証明し、報告した。糖尿病発症抑制研究の道筋を示した点で、本研究成果の意義は大きい。