Effets de modifications aiguës de l'insulinémie endogène sur la distribution subcellulaire des récepteurs de l'insuline dans le foie de rat

Abstract

The effects of acute changes in endogenous insulinemia on the number and subcellular distribution of insulin receptors in rat liver have been studied. After injecting stimulants or inhibitors of insulin secretion, we examined various subcellular fractions from male rats (200 g) for their ability to specifically bind 125I-insulin. Glucose (300 mg) elevated plasma insulin 4 to 6-fold and increased the number of insulin receptors in Golgi fractions by 50%; it decreased the number of receptors in plasma membrane by 20%. These changes were maximal by 5-15 min and reversible in one hour. Arginine (200 mg), glucagon (75 micrograms) and tolbutamide (10 mg), which elevated insulinemia to the same extent as glucose, also increased insulin binding to Golgi fractions. Conversely, somatostatin (40 micrograms) and diazoxide (10 mg), which lowered plasma insulin 3 to 4-fold, decreased insulin binding to Golgi fractions by 20-25%. In all cases, the total number of receptors measured on a crude particulate fraction was not affected. Thus, acute changes in endogenous insulinemia caused a redistribution of insulin receptors in hepatocytes. It is suggested that this redistribution resulted from changes in the internalization rate of the receptors, which itself was a function of the degree of receptor occupancy.