Regulation of beta cell fate during dedifferentiation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08866
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Gunma University
• Principal Investigator: Shirakawa Jun 群馬大学, 生体調節研究所, 教授 (70625532)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病 / 膵β細胞 / 代謝学 / 内分泌学

Outline of Final Research Achievements

A major pancreatic beta cell damage in diabetes is the dedifferentiation of beta cells and transdifferentiation into non-beta islet cells such as alpha cells. However, it has been unknown how beta cells differentiate and how cell fate is determined. In this study, we investigated molecular mechanisms underlying cell fate determination that induce pancreatic alpha, delta, and PP cells in the process of beta cell transdifferentiation in diabetes conditions. As a result, we elucidated the mechanism mediated by the sympathetic nervous system that determines the direction of transdifferentiation of beta cells in the pancreatic tissue.

Free Research Field

代謝・内分泌学

Academic Significance and Societal Importance of the Research Achievements

本研究は、膵β細胞が、膵α細胞になるのか、膵PP細胞になるのかという、膵β細胞分化転換における細胞運命決定の分子機構を明らかにするという既存の概念にはない膵β細胞機能不全のメカニズムに迫ることができた。糖尿病における膵β細胞の障害過程において、それぞれのサブタイプにおける膵β細胞の細胞運命決定の分子機構が解明されると、この分化転換を制御することがで、糖尿病状態において機能的な膵β細胞量の維持ならびに増加につながると考えられ、糖尿病発症・進展過程における新規治療法の開発に寄与するものと期待される。