Elucidation of molecular mechanisms of the liver-beta cell inter-organ neuronal network

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03706
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tohoku University
• Principal Investigator: Imai Junta 東北大学, 医学系研究科, 准教授 (80431500)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 膵β細胞 / 迷走神経 / インスリン / 肥満症

Outline of Final Research Achievements

Previously, we discovered that, during obesity development, pancreatic vagal nerve signals, elicited by liver-β cell inter-organ neuronal network, play critical roles in triggering compensatory β cell proliferation through the FoxM1-dependent mechanism. In this project, we explored the molecular mechanism(s) by which vagal signals activate the β cell FoxM1 pathway. By analyzing mouse isolated islets treated by vagal factors, we identified several transcription factors which is potentially involved in activation of the FoxM1 pathway in β cells. In addition, among these transcription factors, we developed β cell-specific knock-out mice of transcription factor which is abundantly expressed in β cells both in humans and mice.
In addition, we developed mouse model in which inflammation is induced in gastrointestinal tracts, and clarified that the liver-β cell inter-organ neuronal network is activated in these model mice.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究は研究代表者が独自に明らかにした肝臓―膵β細胞間神経ネットワークに着想を得て、この神経ネットワークの未解明の分子機構を明らかにしたものである。本研究結果によってその制御機構がさらに明らかになったことにより、インスリン抵抗性状態における代償性膵β細胞増殖という糖代謝恒常性維持においてきわめて重要なメカニズムの理解が進むことが期待される。
また、膵β細胞を増量する治療法は存在せず、これは糖尿病根治療法開発が進まない大きな要因となっている。本研究結果によって本来生物の体の中にあるシステムを活用した世界で初めての膵β細胞増量薬の開発につながる可能性がある。