Abstract
We have studied insulin binding to cultured skin fibroblasts from a patient with the Type A syndrome of insulin resistance and acanthosis nigricans. Insulin binding was decreased about 50% at low insulin concentrations. This was due to a decrease in receptor affinity and an increase in the rate of dissociation of insulin from the receptor. In addition, there was a loss of negative cooperativity, as measured by the atility of unlabeled insulin to accelerate dissociation. This defect in the receptor was stable for up to 16 passages of the cells. By contrast, binding of epidermal growth factor did not differ from control. These data suggest that the Type A syndrome of insulin resistance is due to a primary, and possibly genetic, defect in the insulin receptor.

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