The role of glutamate signaling in amplification of insulin secretion by cAMP

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461351
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Kobe University
• Principal Investigator: TAKAHASHI HARUMI 神戸大学, 医学(系)研究科(研究院), 特命講師 (50546489)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病 / インスリン分泌 / インクレチン / cAMP

Outline of Final Research Achievements

In this study, we investigated the role of glutamate signaling in incretin-induced insulin secretion. The increase in glutamate content in insulin granules by GLP-1 was protein kinase A-dependent. Glutamate transport into insulin granules through vesicular glutamate transporter 1 was required for amplification of insulin secretion by incretin/cAMP signaling. Dimethyl-glutamate, a membrane-permeable glutamate precursor, augmented glucose-induced insulin granule exocytosis. The analyses using pancreatic islets from animal models of diabetes and obesity indicated that glutamate production by glucose metabolism is associated with incretin-responsiveness. These results suggest the significant role of glutamate signaling in the pathophysiology of diabetes.

Free Research Field

医歯薬学