Regulatory mechanism of mTORC1 activity in pancreatic beta cells in the development of type 2 diabetes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08860
• 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: Kobe University
• Principal Investigator: Asahara Shun-ichiro 神戸大学, 医学部附属病院, 助教 (00570342)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 膵β細胞 / 可塑性 / mTORC1 / 糖尿病

Outline of Final Research Achievements

Although the mechanism of pancreatic β-cell volume reduction has not yet been elucidated, mTORC1 activation in islets of type 2 diabetes patients is thought to be involved. In this study, we analyzed pancreatic β-cell-specific TSC2 knockout (βTSC2KO). βTSC2KO showed an increase in chromogranin A-positive and islet hormone-negative cells, suggesting a differentiation effect. βTSC2KO islets showed amylase-positive cells, which were associated with the exocrine cells, and co-positivity of Ptf1a and chromogranin A, a transcription factor of exocrine cells, was also observed. These results suggest that homeostatic activation of mTORC1 may cause a decrease in β-cells by converting them into exocrine cells in old age.

Free Research Field

糖尿病・代謝学

Academic Significance and Societal Importance of the Research Achievements

糖尿病は1型、2型いずれにおいても、膵β細胞量が発症において重要な因子となる。膵β細胞量減少機序については、これまでに多くの報告があるが、いまだに臨床応用されるようなものはない。代表者は糖尿病膵島でmTORC1が活性化されていることに注目し、mTORC1活性調節を制御することが出来れば、1型糖尿病の根治や2型糖尿病の発症予測ができるのではないかと考えた。本研究を進展させることによって、将来的な膵β細胞不全の治療・予防につながるものと期待している。