GLUCOCORTICOIDS ANTAGONIZE INSULINS ANTIPROTEOLYTIC ACTION ON SKELETAL-MUSCLE IN HUMANS

Although chronic glucocorticoid elevations cause net skeletal muscle p rotein loss in man, the kinetic mechanisms responsible for this catabo lic effect and the capacity of insulin to overcome it remain unclear. To examine this issue, we measured basal and insulin-stimulated rates of protein synthesis and breakdown in muscle using the phenylalanine f orearm kinetic method in eight normal volunteers studied postabsorptiv ely and after 4 days of dexamethasone treatment (8 mg/day). To avoid t he confounding effects of systemic insulinization, local forearm insul in levels were raised by similar to 430 pmol/L using a 150-min brachia l arterial infusion of insulin (0.251 pmol/kg.min). Postabsorptively, dexamethasone produced mild hyperglycemia (P < 0.003) and a 3-fold ris e in plasma insulin (P < 0.001), but no change in forearm phenylalanin e balance or kinetics. Before dexamethasone treatment, local hyperinsu linemia increased forearm glucose uptake 2.5-fold and caused a positiv e net balance of phenylalanine due to a marked 40% inhibition of prote olysis. After dexamethasone treatment, forearm glucose uptake was mode stly reduced. However, forearm net phenylalanine balance remained nega tive due to a striking reduction in insulin's inhibitory effect on pro teolysis. We conclude that 1) the effects of glucocorticoid on basal m uscle protein turnover are minimized by compensatory hyperinsulinemia, and 2) glucocorticoids cause muscle resistance to insulin's antiprote olytic action.