Comprehensive analysis of the mechanisms of pancreatic beta cell proliferation by vagal nerve signals for therapeutic application

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16221
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Tohoku University
• Principal Investigator: Izumi Tomohito 東北大学, 大学病院, 助教 (80747064)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 迷走神経 / 膵β細胞 / 肝臓 / 再生医療

Outline of Final Research Achievements

In this project, we explored the molecular mechanisms of vagal nerve signal-mediated cell proliferation and organ regeneration and its therapeutic potential in pancreatic beta cells and the liver. First, we applied a tissue-clearing technology to the pancreas in order to analyze the anatomy of the vagal nerve system within the pancreas. We found that many of intra-pancreatic parasympathetic ganglia are located in the vicinity of islets. Next, we tested whether vagal nerve signals could induce beta cell proliferation in aged animals, in which cell proliferation capacity is known to be severely restricted. We found that high fat diet feeding promoted beta cell proliferation and increased beta cell mass through vagal nerve signals even in aged mice. Moreover, we clarified that vagal nerve signals are critically involved in liver regeneration after partial hepatectomy and elucidated the molecular mechanism by which vagal nerve signals induce hepatocyte proliferation.

Free Research Field

代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究では、研究代表者が所属するグループが見出した神経シグナルを介した細胞増殖誘導機構と、それによる生体の恒常性維持機構の詳細について、膵β細胞と肝臓を用いて明らかにした。神経シグナルによる細胞増殖機構を臨床に応用することで、高齢者に多い膵β細胞が減少することで発症する糖尿病や、肝臓切除後の肝不全などに対する有望な予防、治療法の開発につながることが期待される。