Metabolic features of hormone secreting cells in pancreatic islets and analyses of their dysfunction using pseudo-islets

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08918
• 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: Nihon University
• Principal Investigator: ISHIHARA Hisamitsu 日本大学, 医学部, 教授 (60361086)
• Co-Investigator(Kenkyū-buntansha): 小須田 南 日本大学, 医学部, 助手 (40811609)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: pancreatic beta-cells / pancreatic alpha-cells / glucose metabolism / metabolic reprogramming

Outline of Final Research Achievements

By analyzing effects of modulation of expression levels of several enzymes constituting the TCA cycle in insulin secreting MIN6 cells, we have suggested that glutamate is important for the metabolism-secretion coupling in insulin secretion evoked by glucose. We have also identified Sox11 as a transcription factor regulating general glucose metabolism in insulin secreting cells. Since Sox11 is known to be a factor important for the epithelial mesenchymal transition, Sox11 may be important for metabolic reprogramming in cell fate determination in insulin secreting cells.
In addition, we successfully generated pseudo-islets from insulin secreting MIN6 cells and glucagon secreting aTC1 cells. Our analyses suggested that the two cell types establish a specific configuration in the cell clusters, which may be important for their hormone secreting properties.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、膵β細胞のインスリン分泌機構の解明を進めるもので、ひいてはインスリン分泌を増強させる薬剤の開発につながる。インスリン分泌を増強する場合には、β細胞の疲弊をもたらさないことが重要であるが、本研究ではインスリン分泌と細胞の運命の両者を制御する因子の候補が見出された。このような因子の存在は、β細胞の疲弊無しにインスリン分泌を増強する薬剤の開発の第一歩となるものである。このターゲットを修飾する食品成分の同定ができれば、2型糖尿病発症・進展予防の食事戦略の開発にもつながる。さらに、偽膵島を用いた解析は、複数の構成細胞からなる膵島のホルモン分泌メカニズムの解明に展開できると考えられる。