Testosterone increases GLUT4‐dependent glucose uptake in cardiomyocytes

Abstract Testosterone exerts important effects in the heart. Cardiomyocytes are target cells for androgens, and testosterone induces rapid effects via Ca2+ release and protein kinase activation and long‐term effects via cardiomyocyte differentiation and hypertrophy. Furthermore, it stimulates metabolic effects such as increasing glucose uptake in different tissues. Cardiomyocytes preferentially consume fatty acids for ATP production, but under particular circumstances, glucose uptake is increased to optimize energy production. We studied the effects of testosterone on glucose uptake in cardiomyocytes. We found that testosterone increased uptake of the fluorescent glucose analog 2‐(N‐(7‐nitrobenz‐2‐oxa‐1, 3‐diazol‐4‐yl)amino)‐2‐deoxyglucose and [3H]2‐deoxyglucose, which was blocked by the glucose transporter 4 (GLUT4) inhibitor indinavir. Testosterone stimulation in the presence of cyproterone or albumin‐bound testosterone induced glucose uptake, which suggests an effect that is independent of the intracellular androgen receptor. To determine the degree of GLUT4 cell surface exposure, cardiomyocytes were transfected with the plasmid GLUT4myc‐eGFP. Subsequently, testosterone increased GLUT4myc‐GFP exposure at the plasma membrane. Inhibition of Akt by the Akt‐inhibitor‐VIII had no effect. However, inhibition of Ca2+/calmodulin protein kinase (CaMKII) (KN‐93 and autocamtide‐2 related inhibitory peptide II) and AMP‐activated protein kinase...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: Original Research Article Source Type: research