sirt1 regulates pancreatic A cell proliferation and glucagon secretion

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K20901
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics; Endocrinology
• 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): 2015-04-01 – 2017-03-31
• Keywords: グルカゴン / Sirt1

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