Session: SUN 203-235-Steroid Hormone Actions, Biosynthesis and Metabolism (posters)
Bench to Bedside
Poster Board SUN 230
Methods HepG2 cells cultured in hyperglycaemic conditions were used to investigate the effects of 24h testosterone treatment (10nM, 100nM) on glucose uptake with or without androgen receptor (AR) blockade (flutamide). Metformin treatment (5μM, 10μM) combined with and without testosterone was studied. The expression of key regulatory targets of glucose uptake and metabolism were assessed by qPCR and western blot. Cellular bioenergetics were analysed by XF metabolic assays (Seahorse Bioscience).
Results -Glucose uptake was increased by approximately 20% in testosterone treated cells and equivalent to the effect of metformin. Combined metformin and testosterone treatment had no additive effect. Flutamide had no effect on testosterone action on glucose uptake. Glucose transporter-2 (GLUT2) expression was increased by testosterone treatment as were the regulatory glycolytic enzymes glucokinase and phosphofructokinase and glycogen synthase. G6PD the regulatory enzyme in the pentose phosphate shunt pathway was decreased by testosterone treatment. Testosterone increased extracellular acidification rate as an indicator of changes in the rate of glycolysis.
Conclusion-Testosterone stimulates glucose utilisation in hepatocytes which is comparable to the efficacy of metformin. This study suggests that testosterone mediates this action by up-regulating the expression of GLUT2, regulatory enzymes of glycolysis combining to increase the rate of glycolysis and potentially storage of glycogen. These effects are AR-independent and have a rapid onset of effect. These findings may in part explain the beneficial effect of testosterone on insulin resistance in men with metabolic syndrome and/or T2D.
Nothing to Disclose: DMK, SA, EM, THJ
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