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Effect of metformin on pancreatic beta cells

Research Project

Project/Area Number 17K16152
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Metabolomics
Research InstitutionYokohama 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
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsメトホルミン / 膵β細胞 / 糖尿病
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.

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。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (4 results)

All 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] Signaling between pancreatic beta-cells and macrophages via S100 calcium-binding protein A8 exacerbates beta-cell apoptosis and islet inflammation.2018

    • Author(s)
      Inoue H, Shirakawa J, Togashi Y, Tajima K, Okuyama T, Kyohara M, Tanaka Y, Saisho Y, Yamada T, Shibue K, Kulkarni RN, Terauchi Y
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 293 Issue: 16 Pages: 5934-5946

    • DOI

      10.1074/jbc.m117.809228

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of metformin on compensatory pancreatic β-cell hyperplasia in mice fed a high-fat diet.2017

    • Author(s)
      Tajima K, Shirakawa J, Okuyama T, Kyohara M, Yamazaki S, Togashi Y, Terauchi Y.
    • Journal Title

      Am J Physiol Endocrinol Metab

      Volume: 313 Issue: 3 Pages: E367-E380

    • DOI

      10.1152/ajpendo.00447.2016

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolic recovery of lipodystrophy, liver steatosis, and pancreatic β cell proliferation after the withdrawal of OSI-9062017

    • Author(s)
      Tajima K, Shirakawa J, Togashi Y, Yamazaki S, Okuyama T, Kyohara M, Konishi H, Terauchi Y.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 4119-4119

    • DOI

      10.1038/s41598-017-04304-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] メトホルミンは、インスリン抵抗性とは独立して、膵β細胞に保護的に作用する2017

    • Author(s)
      田島一樹, 白川純, 富樫優, 寺内康夫
    • Organizer
      第31回日本糖尿病・肥満動物学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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