Dataset Information

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

ABSTRACT:

Background

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.

Method

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.

Results

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-GSK3? (Ser-21), and P-AKT (Ser-473) levels as compared to the control animals; but there was no significant change in total AKT and GSK3?. Testosterone supplementation inhibited GSK3? in the myocytes in a PI3K/AKT pathway dependent manner; on the other hand GSK3? gene expression was reduced in the skeletal muscle upon testosterone supplementation.

Conclusion

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.

SUBMITTER: Pal M

PROVIDER: S-EPMC6834245 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Pal Madhuraka M Khan Jasim J Kumar Ravi R Surolia Avadhesha A Gupta Sarika S

PloS one 20191106 11

<h4>Background</h4>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 gluco ...[more]

PMID: 31693697

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Dataset Information

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

Background

Method

Results

Conclusion

Publications

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

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