Prostasin promotes insulin secretion in pancreatic beta-cells

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17958
• 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: University of Yamanashi
• Principal Investigator: ISHII Toshihisa 山梨大学, 大学院総合研究部, 臨床助教 (50835957)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: プロスタシン / インスリン分泌 / 膵β細胞

Outline of Final Research Achievements

To clarify the role of prostasin (PRSS8) in pancreatic beta-cells, we compared insulin secretion in pancreatic beta cell-specific PRSS8 knockout and overexpression mice, or PRSS8 suppressed and overexpressed mouse insulinoma cell line MIN6 cells. We found that PRSS8 promoted insulin secretion. However Ca2+ uptake was suppressed in PRSS8 knockdown MIN6 cells, PRSS8 had no directly effect on voltage-dependent Ca2+ channels. New substrates of PRSS8 should be explored in the future. On the other hand, the expression of PRSS8 was regulated in a glucose-dependent manner, suggesting that PRSS8 plays an important role in the regulation of insulin secretion.

Free Research Field

内分泌、糖尿病、腎臓

Academic Significance and Societal Importance of the Research Achievements

本研究によって膵β細胞プロスタシンのインスリン分泌機機構における生理的意義及び糖尿病における病態的意義が明らかになりつつある．血糖依存的に発現調節されるプロスタシンはインスリン分泌を改善させる新規治療ターゲットとして合理的な発現調節機構を有していると考えられる．本研究のさらなる追求によって糖尿病に関する新たな病態解明や新規治療開発へとつながることが期待される．