Improvement of functionality by heterogeneity formation of the iPS-derived pancreatic beta cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19543
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Kume Shoen 東京工業大学, 生命理工学院, 教授 (70347011)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: インスリン / 内分泌 / 膵臓 / 機能維持

Outline of Final Research Achievements

We identified TH (dopamine synthase) as a candidate gene involved in heterogeneity in mouse pancreatic β cells. To examine the underlying molecular mechanism of the heterogeneity of beta cells, we performed forced expression of TH in mouse pancreatic β cells. We mixed it with normal pancreatic islet cells at a certain ratio. We then evaluated pancreatic islets' glucose-stimulated insulin secretion (GSIS) ability with or without overexpressing TH. As a result, we found that overexpression of TH in the beta cells lowered the GSIS ability. However, pancreatic islets containing a certain proportion of islet cells expressing TH maintained their GSIS ability for longer. From this result, We therefore concluded that heterogeneity confers pancreatic β cells to preserve their function.

Free Research Field

代謝内分泌

Academic Significance and Societal Importance of the Research Achievements

膵臓内分泌β細胞は血糖の恒常性維持において重要な役割を果たしている。糖尿病における膵臓β細胞の機能低下の一つの成因として、脱分化が考えられるようになってきた。脱分化による臓器の機能低下は膵臓β細胞のみならず、他の臓器にも共通して見られた現象であり、その意義と分子機序の解明が急がれる。一方、膵臓β細胞における不均一性 (ヘテロ性) が報告され、その意義が不明である。本研究では、分化・脱分化、ヘテロ性に関与する遺伝子群の作用機序の解明をめざし、将来それを応用したiPS細胞由来膵臓β細胞のヘテロ性付与による機能向上を目指している。