Changes in the subcellular distribution of insulin receptors in rat liver induced by acute endogenous hyperinsulinemia.

The effects of an acute increase in endogenous plasma insulin on the subcellular distribution of the insulin receptors in rat liver have been examined. Plasma membranes, Golgi fractions, and a total particulate fraction have been prepared in rats (BW, 200 g) various times after the injection of glucose (300 mg), arginine (200 mg), glucagon (75 micrograms), and tolbutamide (10 mg). These fractions have been examined for their ability to bind [125I]insulin after solubilization by Triton X-100. The injection of glucose, which causes a 5-fold elevation in the plasma insulin concentration, results in a 20-25% decrease in insulin binding to plasma membranes and, reciprocally, a 50-70% increase in insulin binding to Golgi fractions; insulin binding to the total particulate fraction is unaffected. These changes achieve maximum at 5-15 min, coinciding with the insulin peak, and undergo complete reversal in 1 h. The enhanced insulin-binding activity in Golgi fractions results almost exclusively from an increase in receptor number. Glucose-induced hyperinsulinemia also results in a 5-fold increase in the insulin content of Golgi fractions at 15 min. Other stimulants of insulin secretion, which elevate insulinemia to the same extent as glucose, also increase insulin binding to Golgi fractions and decrease insulin binding to plasma membranes, with no change in binding activity in the total particulate fraction. It is concluded that an acute increase in the plasma insulin concentration, induced by physiological stimuli, results in a rapid and reversible translocation of the insulin receptors from the surface to the interior of the hepatocyte without affecting their total number.