Dataset Information

Testosterone Increases the Expression and Phosphorylation of AMP Kinase ? in Men With Hypogonadism and Type 2 Diabetes.

ABSTRACT:

Context

Adenosine 5'-monophosphate-activated protein kinase-? (AMPK?) is a mediator of exercise-induced glucose uptake in skeletal muscle.

Objective

We evaluated whether AMPK? expression and phosphorylation are reduced in skeletal muscle and adipose tissue of patients with hypogonadotropic hypogonadism (HH), and whether testosterone replacement therapy results in restoration of the expression and phosphorylation of AMPK?.

Design

This is a secondary analysis of a previously completed trial that showed an insulin-sensitizing effect of testosterone therapy in men with type 2 diabetes and HH.

Setting

Clinical research center at university.

Patients

Thirty-two men with HH and 32 eugonadal men were compared at baseline.

Interventions

Men with HH were treated with intramuscular injections of testosterone or placebo every 2 weeks for 22 weeks. Quadriceps muscle biopsies and subcutaneous abdominal fat biopsies were obtained before and after 4-hour euglycemic hyperinsulinemic clamp, prior to and after testosterone or placebo therapy.

Outcome measures and results

mRNA expression of AMPK? in hypogonadal men was lower by 37% in adipose tissue and 29% in skeletal muscle, respectively, compared with levels in eugonadal men, while phosphorylated AMPK? was lower by 22% and 28%, respectively. Following testosterone replacement, the expression of AMPK? did not alter in the fasting state but increased markedly by 41% and 46% in adipose tissue and muscle, respectively, after the clamp. In contrast, phosphorylated AMPK? increased by 69% in muscle after testosterone therapy but did not change following the clamp.

Conclusions

Testosterone modulates the expression of AMPK? and phosphorylated AMPK?. These effects may contribute to the improved insulin sensitivity following testosterone therapy.

SUBMITTER: Ghanim H

PROVIDER: S-EPMC7077952 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Testosterone Increases the Expression and Phosphorylation of AMP Kinase α in Men With Hypogonadism and Type 2 Diabetes.

Ghanim Husam H Dhindsa Sandeep S Batra Manav M Green Kelly K Abuaysheh Sanaa S Kuhadiya Nitesh D ND Makdissi Antoine A Chaudhuri Ajay A Sandhu Sartaj S Dandona Paresh P

The Journal of clinical endocrinology and metabolism 20200401 4

<h4>Context</h4>Adenosine 5'-monophosphate-activated protein kinase-α (AMPKα) is a mediator of exercise-induced glucose uptake in skeletal muscle.<h4>Objective</h4>We evaluated whether AMPKα expression and phosphorylation are reduced in skeletal muscle and adipose tissue of patients with hypogonadotropic hypogonadism (HH), and whether testosterone replacement therapy results in restoration of the expression and phosphorylation of AMPKα.<h4>Design</h4>This is a secondary analysis of a previously ...[more]

PMID: 31858126

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