In vitro suppression of insulin-mediated amino acid uptake in uremic skeletal muscle.

Resistance to insulin-mediated glucose uptake is well documented in uremia. We have previously reported that in vivo resistance to insulin mediated amino acid uptake is present in the skeletal muscle of acutely uremic rats. This report compares the effect of insulin on in vitro 14C alpha-amino isobutyric acid and cycloleucine uptake by skeletal muscle from uremic and control rats. Intracellular accumulation of 14C alpha-amino isobutyric acid were normal in the diaphragm and epitrochlear muscle of acutely uremic rats in the absence of insulin. However, insulin failed to further stimulate amino acid uptake in both tissues. Insulin also failed to stimulate cellular uptake of cycloleucine in skeletal muscle from acutely uremic animals. Resistance to insulin-mediated amino acid uptake was evident in rats with chronic uremia. This resistance to insulin mediated increases in intracellular amino acid concentration may contribute to the abnormal depression in protein synthesis or the exaggerated gluconeogenesis and alanine turnover seen in uremia.