Physiological role of pancreatic incretin on the functional regulation of pancreatic islet cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461350
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kawasaki Medical School
• Principal Investigator: Kaku Kohei 川崎医科大学, 医学部, 教授 (10116709)
• Research Collaborator: NAKASHIMA Koji ; KIMURA Tomohiko ; HIRUKAWA Hidenori ; OKAUCHI Seizo ; OBATA Atsushi ; KANETO Hideaki ; SHIGETO Makoto ; Rorsman Patrik
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 糖尿病 / 膵ラ氏島機能 / 膵灌流 / 膵インクレチン / 膵α細胞 / GLP-1 / GLP-1受容体 / autocrine作用

Outline of Final Research Achievements

To assess a physiological role of pancreatic GLP-1 on the regulation of pancreatic islet cell function, GLP-1 secretion by using pancreas perfusion study and GLP-1 receptors (GLP-1Rs) in islet cells by immunohistochemical analysis were investigated in non-diabetic and diabetic rats.
The perfusion study of diabetic GK rats demonstrated a significant secretion of GLP-1 from the pancreas. GLP-1Rs were observed in α-cells in diabetic GK rats, but not in non-diabetic rats. Exendin-4 stimulated both glucagon and GLP-1 secretions from α-cells and cAMP-dependent insulin secretion from β-cells. In addition, the immunostochemical analysis revealed that GLP-1/GLP-1R complex induced the endosome formation in pancreatic α-cells of diabetic rats.
These results strongly suggested the existence of autocrine mechanism of GLP-1/GLP-1R in pancreatic α-cells of diabetic rats, by which the deranged islet function in diabetic condition might be restored.

Free Research Field

医歯薬学