The finding of glucose metabolism improver derived from skeletal muscle

• Project/Area Number: 16K01812
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Gunma University
• Principal Investigator: SAITO TSUGUMICHI 群馬大学, 大学院医学系研究科, 助教 (80572619)
• Research Collaborator: SAITO HARUKA
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 細胞外小胞 / 骨格筋 / 脂肪細胞 / 伸展刺激 / 糖取り込み / インスリン / インスリン感受性 / メカノトランスダクション / 糖尿病

Outline of Final Research Achievements

We found that the extracellular vesicles (EVs) from skeletal muscle are continuously secreted in medium. Interestingly, we confirmed that only these EVs secreted during mechanical stretched condition promote insulin-stimulated glucose uptake in not only muscle cells, but also in adipocytes, without any effects on insulin signaling. Furthermore, these EVs increased the expression of glucose transporter 4 (Glut4) in adipocytes. Because EVs increased glucose uptake in similar manner with exercise, we speculated that these findings may explain the mechanism of the exercise effect on glucose homeostasis in vivo. Based on these findings, we are going to next step to find the real improver for diabetes mellitus.

Academic Significance and Societal Importance of the Research Achievements

糖尿病は食事療法、運動療法が治療の中心である。しかし、高齢、糖尿病合併症、運動器の機能不全などの理由により運動療法を享受できない患者数は相当数にのぼる。我々の発見が運動療法を模倣するのであれば、これら多くの患者に自己の細胞から細胞外小胞を人為的に増幅させ、新規の糖尿病として用いることが出来るのではないかと考えている。そのため本研究成果が糖代謝機構の解明にとどまらず、新規糖尿病治療法に繋がる可能性がある。

Research Products

• [Journal Article] APPL1 promotes glucose uptake in response to mechanical stretch via the PKCζ-non-muscle myosin IIa pathway in C2C12 myotubes (2016)
  • Author(s): Tsugumichi Saito, Shuichi Okada, Yoko Shimoda, Yuko Tagaya, Aya Osaki, Eijiro Yamada, Ryo Shibusawa, Yasuyo Nakajima, Atsushi Ozawa, Tetsurou Satoh, Masatomo Mori, and Masanobu Yamada
  • Journal Title: Cellular Signalling Volume: 28 Pages: 1694-1702
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 骨格筋由来細胞外小胞は骨格筋、脂肪細胞での糖取り込み機構を制御する。 (2018)
  • Author(s): 齋藤従道、清水智彦、下田容子、岡田純一、渋澤 良、 笠井裕子、大崎 綾、山田英二郎、岡田秀一、山田正信
  • Organizer: 第61回日本糖尿病学会学術集会
• [Presentation] Mechanical stretch-induced extracellular vesicles (EVs) improved insulin-stimulated glucose uptake in myotubes and adipocytes (2018)
  • Author(s): Tsugumichi Saito, Yoko Shimoda, Hiroyuki Shimizu, Junichi Okada, Ryo Shibusawa, Yuko Kasai, Aya Osaki, Eijiro Yamada, Shuichi Okada, Masanobu Yamada
  • Organizer: 第54回欧州糖尿病学会
  • Int'l Joint Research
• [Presentation] 骨格筋由来細胞外小胞は骨格筋、脂肪細胞での糖取り込み機構を制御する。 (2018)
  • Author(s): 齋藤従道
  • Organizer: 第61回日本糖尿病学会学術集会
• [Presentation] APPL1 affects on glucose uptake induced by mechanical stretch in C2C12 myotubes (2016)
  • Author(s): Tsugumichi Saito, Ryo Shibusawa, Yoko Shimoda, Yuko Tagaya, Aya Osaki, Eijiro Yamada, Shuichi Okada, Masanobu Yamada
  • Organizer: 第17回国際内分泌学会
  • Place of Presentation: 北京（中国）
  • Year and Date: 2016-08-31
  • Int'l Joint Research
• [Presentation] 骨格筋培養細胞を用いた伸展刺激による糖代謝機構の解明 (2016)
  • Author(s): 齋藤従道、澁澤良、下田容子、多賀谷裕子、大崎 綾 山田英二郎、岡田秀一、山田正信
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2016-05-19