Heterogeneity of the insulin-receptor interaction in lipoatropic diabetes

[125] Insulin binding to its receptors was studied on circulating cells from 11 patients (8 females and 3 males) with lipoatropic diabetes. The patients ranged in age from 9-54 yr. All were insulin resistant, as evidenced by fasting hyperinsulinemia and insulin tolerance tests. Nine patients were evaluated by specific [125] insulin binding to monocytes. Three different patterns of receptor abnormalities were observed: 3 patients demonstrated decreased binding due to decreased binding capacity, 2 patients revealed normal tracer binding with decreased receptor affinity,, and 4 patients had normal or increased insulin binding. [125] Insulin binding to erythrocytes in 9 cases demonstrated similar heterogeneities of initial binding. In most cases there was a good correlation between the binding with erythrocytes and monocytes, although decreased affinity was not observed in the red blood cells. There was no obvious correlations between the nature of the receptor defect and the clinical patterns in these patients. Heterogeneity in insulin binding was even observed among affected members of the same family. Antibodies to the insulin receptor were not detected in any of these patients by either binding inhibition or immunoprecipitation assays. These data suggest that the pathogenesis of the insulin resistance in lipoatropic diabetes is heterogeneous and may involve both receptor and postreceptor abnormalities.