Effect of metformin on pancreatic beta cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16152
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Yokohama City University
• Principal Investigator: TAJIMA Kazuki 横浜市立大学, 医学研究科, 客員研究員 (00725236)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: メトホルミン

Outline of Final Research Achievements

The effect of metformin on the pancreatic beta cells under hyperglycemic or endoplasmic reticulum stress conditions were analyzed using high-fat fed mice and pancreatic beta cell lines. Metformin suppressed the compensatory beta cell proliferation in short-term high-fat fed mice, which did not exhibit insulin resistance. Metformin repressed the beta cell proliferation induced by high glucose. Metformin induced the phosphorylation of AMPK and reduced the mTOR signal. Metformin suppressed the apoptosis in beta cells induced by tapsigargin and metformin reduced the translation initiation via 4EBP-1. These results suggested that metformin had protective effect on the pancreatic beta cells independent of the improvement of insulin resistance.

Free Research Field

糖尿病学

Academic Significance and Societal Importance of the Research Achievements

本研究で、メトホルミンによる、インスリン抵抗性とは独立した膵β細胞の保護機構を解明できれば、糖尿病発症前における早期治療の有効性など、糖尿病発症の抑制にもつながる。これは、経済面に多大な影響を及ぼしている糖尿病マネジメントにおいても、社会的な意義があると考えられる。さらには、メトホルミンによる保護機構を明らかにすることで、糖尿病の根本的治療となり得る膵β細胞量の制御機構の解明にも繋がることが期待できる。