Switching mechanisms for pancreatic beta-cell growth

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K08528
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Gunma University
• Principal Investigator: TORII SEIJI 群馬大学, 食健康科学教育研究センター, 教授 (40312904)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: インスリン / 分泌顆粒 / 増殖シグナル / オートクライン / チロシンホスファターゼ

Outline of Final Research Achievements

Phogrin is a transmembrane protein that localizes on secretory granules in pancreatic β-cells. We previously showed that phogrin participates in molecular interactions with insulin receptors (IR) to regulate insulin receptor substrate 2 (IRS2) protein stability and in turn glucose-promoted β-cell growth. Glucose is a principal regulator of β-cell survival and growth as well as insulin secretion. Despite the growing evidence for the significance of the IR/IRS2-mediated signaling pathways in β-cells, whether secreted insulin acts in an autocrine fashion remains controversial. We showed that phogrin-deficient mice fed a fat diet have defects in β-cell compensatory growth. This is likely because phogrin binds to IR only at conditions that are needed for β-cell expansion. We identified a new phogrin partner, and its binding of phogrin inhibits phogrin-IR interactions. This study represents the first report of a switching regulator of autocrine insulin action in pancreatic β-cells.

Free Research Field

内分泌生化学

Academic Significance and Societal Importance of the Research Achievements

膵β細胞は自身が置かれた状況に応じて、分泌インスリンによるオートクライン増殖を行っていることが明確になった。この成果はβ細胞マスの低下が一因である2型糖尿病の予測、そして新たな予防・治療法の開発につながる。