Elucidation of mechanism for activation of glutamate receptor in pancreatic beta-cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K18416
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy; General pharmacology
• Research Institution: National Institute of Advanced Industrial Science and Technology
• Principal Investigator: Murotomi Kazutoshi 国立研究開発法人産業技術総合研究所, 生命工学領域, 主任研究員 (40635281)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: NMDA受容体 / NR2サブユニット / リン酸化 / インスリン / 糖尿病

Outline of Final Research Achievements

In this study, we investigated a mechanism for activation of glutamate receptor, which is involved in secretion of insulin, in pancreatic beta-cells. At first, we measured expression levels of NMDA receptor subunits in murine beta-cell line MIN6 by qRT-PCR. NR1 and NR2D expression levels were higher than that of NR2B and NR2C in MIN6 cells. However, a NR2C/2D specific antagonist PPDA had no effect of insulin secretion in MIN6 cells. Rather, a NR2B specific antagonist Ro 25-6931 significantly increased insulin secretion. In addition, the increased insulin secretion were inhibited by treatement of phophatase inhibitor. These results indicate that insulin is secreted by NMDA receptor NR2B subunit expressed in pancreatic beta-cells and protein phosphorylation may be involved in the process of insulin secretion mediated by NR2B.

Free Research Field

薬理学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

脳に豊富に存在するNMDA酸受容体NR2Bサブユニットを介して、血糖降下ホルモンであるインスリン分泌が促進されることを明らかにした。そのため、NR2Bおよびその活性化に関わるリン酸化シグナルは、新規糖尿病の治療標的となる可能性がある。今後、NR2Bやリン酸化シグナルを標的とする薬が、マウスやヒトの糖尿病に対する有効か否かを検証することで、新規糖尿病治療薬開発に貢献できると考えられる。