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

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

Author information

1
Department of Movement, Human and Health Sciences Section of Health Sciences, Unit of Endocrinology, Università degli Studi di Roma "Foro Italico", 00135, Rome, Italy.
2
Department of Anatomical, Histological, Forensic and Orthopedic Sciences-Section of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy.
3
Department of Experimental and Clinical Medicine, University of Florence, 50134, Florence, Italy.
4
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
5
Department of Movement, Human and Health Sciences Section of Health Sciences, Unit of Endocrinology, Università degli Studi di Roma "Foro Italico", 00135, Rome, Italy. clara.crescioli@uniroma4.it.

Abstract

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

PMID:
28508346
PMCID:
PMC5610223
DOI:
10.1007/s40618-017-0686-y
[Indexed for MEDLINE]
Free PMC Article

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