Increased affinity of insulin receptor on hepatocytes from streptozotocin-induced diabetic rats

When we use Scatchard analysis for insulin receptor on intact cells, internalization of insulin may affect the Scatchard analysis. In this study, results from Scatchard analysis for insulin receptor on hepatocytes of streptozotocin (STZ)-induced diabetic rats were compared with those from association and dissociation studies and those from Scatchard analysis using hepatocyte membrane which does not internalize insulin. Insulin binding was increased in both hepatocytes and the membranes from STZ-treated rats. Scatchard analysis revealed that both the receptor number and affinity constant were increased. In the dissociation study, the increase in the affinity constant was revealed to be due to a decrease in the dissociation rate constant. The association rate constant was comparable in STZ and control rats. The Scatchard plot was more concave in STZ rats than in controls, suggesting that the magnitude of the negative cooperative effect was greater in STZ rats. This was confirmed by measuring the dissociation rate constant in the presence or absence of unlabeled insulin. Increases in the receptor number, affinity constant, and negative cooperative effect in STZ rats were observed both in hepatocytes and in hepatocyte membranes.