Effect of dehydroepiandrosterone on insulin action and development of insulin-induced resistance in C2C12 muscle cells

Abstract Dehydroepiandrosterone (DHEA), a precursor of androgens and estrogens, has been demonstrated to have effect of preventing insulin resistance and development of diabetes mellitus. Administration of testosterone appears to induce a marked insulin resistance. How these two hormones affect insulin resistance through regulation of sensitivity of tissues to insulin deserves further studies. Here, the effects of DHEA and testosterone on response to insulin in C2C12 muscle cells are analyzed. After 24 h of DHEA (10−6 mol/L) treatment, C2C12 cells showed an increased insulin- stimulated glucose uptake and enhanced activities of glycogen synthase (GS),phosphofructokinase (PFK) and pyruvate dehydrogenase (PDH), whereas testosterone gave the opposite effects. Incubation of C2C12 cells with high-dose insulin (5 × 10−7 mol/L) for 24 hours decreased their sensitivity to insulin and led to a state of resistance as assessed on insulin-stimulated glucose uptake and activities of GS, PFK and PDH. Addition of DHEA t...