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Molecular basis of exercise-induced improvement of insulin resistance

Research Project

Project/Area Number 20K20620
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionWaseda University

Principal Investigator

AKIMOTO Takayuki  早稲田大学, スポーツ科学学術院, 教授 (00323460)

Co-Investigator(Kenkyū-buntansha) 加藤 義雄  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ長 (20415657)
狩野 豊  電気通信大学, 大学院情報理工学研究科, 教授 (90293133)
清水 一憲  名古屋大学, 工学研究科, 准教授 (70402500)
Project Period (FY) 2020-07-30 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2023: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2022: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000)
Keywords骨格筋 / メカニカルストレス / 糖輸送体 / グルコース / グルコース動態 / エネルギー代謝 / in vivoイメージング / 三次元培養 / 糖代謝 / インスリン抵抗性
Outline of Research at the Start

定期的で適度な運動がインスリン抵抗性を改善することは古くから知られており,これが糖尿病等の代謝性疾患の治療や予防に運動療法が用いられる科学的根拠となっているが,そのメカニズムはほとんど分かっていない.
本研究では,三次元培養骨格筋組織,糖代謝動態をモニタリング可能なプローブ,動的環境におけるin vivoイメージングを使って,運動によるインスリン抵抗性改善の分子メカニズムに迫る.

Outline of Final Research Achievements

We developed a high-throughput screening system to visualize mechanical stimulus-dependent glucose uptake into skeletal muscle tissues to investigate the molecular mechanism of exercise-induced improvement of insulin resistance and to create a new therapeutic strategy against insulin resistance.
As a result of this study, we established a high-throughput screening on 96-well plates using three-dimensional cultured skeletal muscle tissues. The Glut4 fusion protein with a pH-dependent fluorescent protein developed in this study can be used as a tool to observe the behavior of glucose. Using these tools, it is now possible to observe the dynamics of glucose in skeletal muscle tissue during muscle contraction.

Academic Significance and Societal Importance of the Research Achievements

本研究による知見は,運動によるインスリン抵抗性改善の分子メカニズムを理解するための一助となると考えられる.また本研究で開発したスクリーニングシステムを使って今後,インスリン抵抗性に対する新らしい化合物の探索が可能かもしれない.

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2021 Other

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

  • [Int'l Joint Research] University of Padova/Venetian Institute of Molecular Medicine(イタリア)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Utah/Kansas State University(米国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] In vivo Ca2+ dynamics during cooling after eccentric contractions in rat skeletal muscle.2021

    • Author(s)
      Takagi R, Tabuchi A, Asamura T, Hirayama S, Ikegami R, Tanaka Y, Hoshino D, Poole DC, Kano Y.
    • Journal Title

      Am J Physiol Regul Integr Comp Physiol.

      Volume: 320(2) Issue: 2 Pages: R129-R137

    • DOI

      10.1152/ajpregu.00253.2020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Type I diabetes suppresses intracellular calcium ion increase normally evoked by heat stress in rat skeletal muscle2021

    • Author(s)
      Ikegami Ryo、Eshima Hiroaki、Nakajima Toshiaki、Toyoda Shigeru、Poole David C.、Kano Yutaka
    • Journal Title

      American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

      Volume: 320 Issue: 4 Pages: R384-R392

    • DOI

      10.1152/ajpregu.00168.2020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular Mechanisms of Skeletal Muscle Hypertrophy.2021

    • Author(s)
      Schiaffino S, Reggiani C, Akimoto T, Blaauw B.
    • Journal Title

      J Neuromuscul Dis.

      Volume: 8(2) Issue: 2 Pages: 169-183

    • DOI

      10.3233/jnd-200568

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Remarks] 早稲田大学筋生物学研究室

    • URL

      https://www.waseda.jp/sem-muscle/index.html

    • Related Report
      2020 Research-status Report
  • [Remarks] 電気通信大学狩野研究室

    • URL

      http://www.ecc.es.uec.ac.jp/

    • Related Report
      2020 Research-status Report
  • [Remarks] 国立研究開発法人産業技術総合研究所 バイオメディカル研究部門 構造創薬研究グループ 加藤義雄研究室

    • URL

      https://staff.aist.go.jp/y-kato/

    • Related Report
      2020 Research-status Report

URL: 

Published: 2020-08-03   Modified: 2025-01-30  

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