1. Academic Validation
  2. High glucose inhibits myogenesis and induces insulin resistance by down-regulating AKT signaling

High glucose inhibits myogenesis and induces insulin resistance by down-regulating AKT signaling

  • Biomed Pharmacother. 2019 Dec;120:109498. doi: 10.1016/j.biopha.2019.109498.
Wei Luo 1 Lei Ai 2 Bo-Fa Wang 3 Yue Zhou 4
Affiliations

Affiliations

  • 1 Department of Exercise Physiology, Beijing Sport University, Beijing, China; Department of Sports and Health Sciences, Nanjing Sport Institute, Nanjing, China.
  • 2 Jiangsu Research Institute of Sports Science, Nanjing, China.
  • 3 Department of Exercise Physiology, Beijing Sport University, Beijing, China.
  • 4 Department of Exercise Physiology, Beijing Sport University, Beijing, China. Electronic address: zhouy@bsu.edu.cn.
Abstract

Background: A high glucose level is usually considered to be the factor that induces tissue and cell dysfunction and damage, commonly known as "glucose toxicity".

Objective: This study aimed to explore the effects and the potential molecular mechanisms of high glucose on myoblast differentiation and Insulin sensitivity.

Materials and methods: C2C12 cells were cultured in differentiation medium containing 25, 40, or 60 mM glucose for 1, 3, or 5 days. E-MHC positive area and GLUT4 fluorescence were evaluated through Immunofluorescence. The expression of Myf5, MyoD, myogenin were measured by performing western blot and qRT-PCR. The protein expression of GLUT4 on cell membrane and glucose uptake in C2C12 myotubes were measured through western blot and 2-NBDG assay. Akt Activator SC79 and inhibitor MK2206 was utilized to reveal the important role of Akt signaling in myogenesis and Insulin sensitivity inhibited by high glucose.

Results: 60 mM glucose inhibits myogenesis by decreasing the expression of MyoD and myogenin, and induces Insulin resistance by reducing both basal and insulin-stimulated GLUT4 expressions and glucose uptakes. The influences of high glucose on myogenesis and IR was related to decreased Akt activation. SC79 rescued the inhibition of high glucose on myogenesis and attenuated IR. MK2206 inhibits the myogenic differentiation and induces IR.

Conclusion: The present study reveals that high glucose inhibited myogenisis accompanied by inducing IR, through Akt signaling inhibition, which may help to further research for resisting degenerative muscular diseases caused by glucose metabolism disorders.

Keywords

AKT-GLUT4; High glucose; Insulin resistence; Myoblast; Myogenesis.

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