Testosterone supplementation improves insulin responsiveness in HFD fed male T2DM mice and potentiates insulin signaling in the skeletal muscle and C2C12 myocyte cell line

Autoři: Madhuraka Pal aff001;  Jasim Khan aff002;  Ravi Kumar aff001;  Avadhesha Surolia aff003;  Sarika Gupta aff001
Působiště autorů: Molecular Science Laboratory, National Institute of Immunology, New Delhi, India aff001;  Molecular Toxicology Laboratory, Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, India aff002;  Molecular Biophysics Unit, Indian Institute of Science, Bengaluru, Karnataka, India aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224162



Type 2 Diabetes Mellitus (T2DM) is characterised by hyperglycemia due to the incidence of insulin resistance. Testosterone supplementation has been shown to have a positive co-relation with improved glycemic control in T2DM males. Clinical studies have reported that Androgen Replacement Therapy (ART) to hypogonadic males with T2DM resulted in improved glycemic control and metabolic parameters, but, these studies did not address in detail how testosterone acted on the key glucose homeostatic organs.


In this study, we delineate the effect of testosterone supplementation to high-fat diet (HFD) induced T2DM in male C57BL6J mice and the effect of testosterone supplementation on the skeletal muscle insulin responsiveness. We also studied the effect of testosterone on the insulin signaling pathway proteins in C2C12 myocyte cells to validate the in vivo findings.


We found that testosterone had a potentiating effect on the skeletal muscle insulin signaling pathway to improve glycaemic control. We demonstrate that, in males, testosterone improves skeletal muscle insulin responsiveness by potentiating the PI3K-AKT pathway. The testosterone treated animals showed significant increase in the skeletal muscle Insulin Receptor (IR), p85 subunit of PI3K, P-GSK3α (Ser-21), and P-AKT (Ser-473) levels as compared to the control animals; but there was no significant change in total AKT and GSK3α. Testosterone supplementation inhibited GSK3α in the myocytes in a PI3K/AKT pathway dependent manner; on the other hand GSK3β gene expression was reduced in the skeletal muscle upon testosterone supplementation.


Testosterone increases insulin responsiveness by potentiating insulin signaling in the skeletal muscle cells, which is in contrast to the increased insulin resistance in the liver of testosterone treated T2DM male animals.

Klíčová slova:

Androgens – Gene expression – Glycogens – Insulin – Insulin signaling – Skeletal muscles – Testosterone


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2019 Číslo 11