Insulin and glucagon binding and stimulation of amino acid transport in isolated hepatocytes from streptozotocin diabetic rats.

The binding of insulin and glucagon and the effects of these hormones on amino acid transport were examined in isolated rat hepatocytes from streptozotocin diabetic rats. Hepatocytes from diabetic rats bound more insulin than cells from control animals. These changes were accounted for by a 50%-60% increase in the number of insulin receptors per cell. Glucagon binding did not significantly differ in hepatocytes from both groups. Following a 2 hr incubation of the cells in vitro, the basal rate of alpha-aminoisobutyric acid (AIB) influx was enhanced in diabetic rat hepatocytes compared to controls. This alteration was accounted for by an increase in the Vmax of both a low affinity and a high affinity component of transport. The ability of diabetic rat hepatocytes to respond to maximally stimulating concentrations of insulin or glucagon by enhancing further the rate of AIB influx was markedly diminished. Hormone responsiveness was restored to normal in hepatocytes from insulin-treated diabetic animals. The data suggest that in diabetic rat hepatocytes the diminished insulin and glucagon responsiveness with regard to the stimulation of amino acid transport stems from postreceptor alteration(s).