Invesitigation of GLP-1 mediated pancreatic beta cell proliferation by interactions between islets and acinar cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17516
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Yokohama City University
• Principal Investigator: KYOHARA Mayu 横浜市立大学, 附属病院, 助教 (20828545)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: GLP-1

Outline of Final Research Achievements

GLP-1 enhances cell proliferation in pancreatic β-cells. We conducted a quantitative proteomic analysis of mouse islets treated with GLP-1 receptor agonist liraglutide. Pancreatic exocrine enzymes, such as α-amylase 1 (Amy1), were identified as up-regulated proteins by liraglutide treatment. We also identified that liraglutide augmented the expression of Lithostatin-1 (Reg-1) in islets. Reg-1 predominantly expresses in pancreatic acinar cells, and regulates β-cell proliferation. By co-culture of isolated islets with acinar cells, the expression level of Reg-1, Amy1, and cell adhesion molecules, p-cadherin and connexin-26, were increased by liraglutide treatment in islets. It was suggested that GLP-1 promoted adhesion between islets and surrounding acinar cells, and interaction between islets and acinar cells potentially contributed to the GLP-1-mediated β-cell proliferation through mitotic action of Reg-1 from acinar cells.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

本研究により、GLP-1による膵β細胞増殖における、膵島と腺房細胞との相互作用を介した新規経路の関与が示唆された。本研究の成果はGLP-1等のインクレチンを介した糖尿病治療における未解明の作用機序解明につながるとともに、膵β細胞増殖研究への貢献と、腺房細胞を標的とした糖尿病の新規治療法の開発へとつながる可能性がある。