Comparative study of testosterone and vitamin D analogue, elocalcitol, on insulin-controlled signal transduction pathway regulation in human skeletal muscle cells

J Endocrinol Invest. 2019 Aug;42(8):897-907. doi: 10.1007/s40618-018-0998-6. Epub 2019 Jan 1.

Abstract

Purpose: Skeletal muscle (Skm) plays a key role in regulating energetic metabolism through glucose homeostasis. Several hormones such as Testosterone (T) and Vitamin D (VD) have been shown to affect energy-dependent cell trafficking by determining Insulin (I)-like effects.

Aim: To elucidate possible hormone-related differences on muscular metabolic control, we analyzed and compared the effects of T and elocalcitol (elo), a VD analogue, on the activation of energy-dependent cell trafficking, metabolism-related-signal transduction pathways and transcription of gene downstream targets.

Methods: Human fetal skeletal muscle cells (Hfsmc) treated with T or elo were analyzed for GLUT4 localization, phosphorylation/activation status of AKT, ERK1/2, IRS-1 signaling and c-MYC protein expression.

Results: T, similar to elo, induced GLUT4 protein translocation likely in lipid raft microdomains. While both T and elo induced a rapid IRS-1 phosphorylation, the following dynamic in phosphorylation/activation of AKT and ERK1/2 signaling was different. Moreover, T but not elo increased c-MYC protein expression.

Conclusions: All together, our evidence indicates that whether both T and elo are able to affect upstream I-like pathway, they differently determine downstream effects in I-dependent cascade, suggesting diverse physiological roles in mediating I-like response in human skeletal muscle.

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

Publication types

  • Comparative Study

MeSH terms

  • Androgens / pharmacology
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology
  • Cells, Cultured
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology*
  • Male
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Signal Transduction / drug effects*
  • Testosterone / pharmacology*

Substances

  • Androgens
  • BXL628
  • Hypoglycemic Agents
  • Insulin
  • Testosterone
  • Calcitriol