Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells

J Endocrinol Invest. 2017 Oct;40(10):1133-1143. doi: 10.1007/s40618-017-0686-y. Epub 2017 May 15.


Purpose: Testosterone by promoting different metabolic pathways contributes to short-term homeostasis of skeletal muscle, the largest insulin-sensitive tissue and the primary site for insulin-stimulated glucose utilization. Despite evidences indicate a close relationship between testosterone and glucose metabolism, the molecular mechanisms responsible for a possible testosterone-mediated insulin-like effects on skeletal muscle are still unknown.

Methods: Here we used undifferentiated proliferating or differentiated human fetal skeletal muscle cells (Hfsmc) to investigate the short-term effects of testosterone on the insulin-mediated biomolecular metabolic machinery. GLUT4 cell expression, localization and the phosphorylation/activation of AKT, ERK, mTOR and GSK3β insulin-related pathways at different time points after treatment with testosterone were analyzed.

Results: Independently from cells differentiation status, testosterone, with an insulin-like effect, induced Glut4-mRNA expression, GLUT4 protein translocation to the cytoplasmic membrane, while no effect was observed on GLUT4 protein expression levels. Furthermore, testosterone treatment modulated the insulin-dependent signal transduction pathways inducing a rapid and persistent activation of AKT, ERK and mTOR, and a transient inhibition of GSK3β. T-related effects were shown to be androgen receptor dependent.

Conclusion: All together our data indicate that testosterone through the activation of non-genomic pathways, participates in skeletal muscle glucose metabolism by inducing insulin-related effects.

Keywords: Human skeletal muscle cells; Insulin; Metabolism; Testosterone.

MeSH terms

  • Androgens / pharmacology
  • Biomarkers / metabolism*
  • Cells, Cultured
  • Fetus / drug effects
  • Fetus / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • In Vitro Techniques
  • Insulin / pharmacology*
  • Insulin Resistance
  • Male
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects*
  • Testosterone / pharmacology*


  • Androgens
  • Biomarkers
  • Hypoglycemic Agents
  • Insulin
  • Testosterone