The interaction of insulin with its receptor was studied in purified liver plasma membranes and isolated hepatocytes of the obese hyperglycemic mouse (ob/ob) and its thin litter mate. The ob/ob mouse is a genetic mutant characterized by marked obesity, hyperinsulinism, and resistance to both endogenous and exogenous insulin. Under identical conditions of preparation and incubation, the membranes of the ob/ob mouse bind only 20 to 25% as much insulin per mg of protein as those of their thin litter mates. Scatchard analysis suggests that this decrease in binding is due to a decrease in the number of receptor sites in the membrane of the obese mouse, especially those of higher affinity. The result with isolated hepatocytes was qualitatively the same.

In contrast to the marked decrease in insulin receptors, the membranes of the obese mouse were similar to those of their thin litter mates in activity of membrane marker enzymes, protein subunit structure, and binding of ¹²⁵I-human growth hormone and isoproterenol. There was a decrease in ¹²⁵I-glucagon binding but to a much smaller extent than that observed in insulin binding. The decrease in insulin receptors in the ob/ob mouse correlates well with the insulin resistance which they exhibit.