Insulin receptors on hepatocytes from spontaneously diabetic Chinese hamsters.

Abstract

Insulin receptors on hepatocytes were studied in spontaneously diabetic Chinese hamsters, which are the animal models for insulin deficient diabetes. Insulin binding in diabetic animals increased mainly due to an increase in the number of receptors. Although binding affinity of diabetic animals was similar to that of control animals, a kinetic study revealed that both the association rate constant and the dissociation rate constant decreased in diabetic animals. Negatively cooperative interactions between receptors were demonstrated in control and diabetic animals, and both the magnitude and sensitivity of this effect was the same in both types of animals. A significant inverse correlation between insulin binding and the plasma insulin concentration was found in these animals. These results therefore suggest that there is an increase in the insulin binding in the insulin deficient diabetic state mainly due to an increase in the number of receptors with a decrease in both the association and dissociation rate constants, and these changes may be important in the altered metabolic state.