Sirt1 regulates pancreatic alpha cell proliferation and glucagon secretion

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08970
• 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: Gunma University
• Principal Investigator: Kikuchi Osamu 群馬大学, 生体調節研究所, 研究員 (40739009)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: グルカゴン / Sirt1 / 膵α細胞

Outline of Final Research Achievements

Sirt1, known as an energy sensor, regulates pancreatic β cell proliferation and insulin secretion However, the roles of Sirt1 in α cells are still unclear. Thus, we investigated the roles of Sirt1 in α cell proliferation and glucagon secretion.
We generated α cell specific Sirt1 knockout(αSKO) mice. α cell mass in αSKO mice was significantly increased compared to the control mice. Although recovery from insulin-induced hypoglycemia was impaired in αSKO mice due to decreased plasma glucagon secretion. Hyperinsulinemic-hypoglycemic clamp revealed that αSKO mice have lower hepatic glucose production (HGP) and lower plasma glucagon concentration than the control mice at 60 min after insulin injection. However, at 120 min after insulin injection, HGP and plasma glucagon concentration were rather increased in αSKO mice compared to the control mice. These results suggest that Sirt1 inhibits α cell proliferation, whereas accelerates glucagon secretion in α cells.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

近年、糖尿病病態におけるグルカゴンの役割は重要視されつつある。糖尿病で見らえるグルカゴン分泌異常のメカニズムの一部を解明した本研究の学術的意義は大きい。また、グルカゴンをターゲットとした糖尿病治療薬の分子標的としてSirt1やその下流因子を同定出来たことは社会的な意義も大きい。