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Journal of Clinical Endocrinology & Metabolism Vol. 52, No. 3 416-425
doi:10.1210/jcem-52-3-416
Copyright © 1981 by the Endocrine Society.
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Heterogeneity of the Insulin-Receptor Interaction in Lipoatropic Diabetes*

HELENA WACHSLICHT-RODBARD, MICHELE MUGGEO, C. RONALD KAHN, GEORGE A. SAVIOLAKIS, LEN C. HARRISON and JEFFREY S. FLIER

Diabetes Branch, National Institute of Arthritis, Metabolism, and Digestive Diseases, National Institutes of Health Bethesda, Maryland 20205

Address requests for reprints to: Dr. C. Ronald Kahn, Cellular and Molecular Physiology Section, Diabetes Branch, National Institute Arthritis, Metabolism, and Digestive Diseases, Building 10, Room 85-243, National Institutes of Health, Bethesda, Maryland 20205.

[125I]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 [125II]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 receptoraffinity, and 4 patients had normal or increased insulin binding. [125II]Insulin binding to erythrocytes in 9 cases demonstrated similar heterogeneities of initial binding. In most cases there was good correlation between the binding with erythrocytes and monocytes, although decreased affinity was not observed in the red blood cells. There was no obvious correlation between the nature ofthereceptor defect and the clinicalpatterns 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.

* Presented in part at the 36th Annual Meeting of the American Federation for Clinical Research, Washington, D. C, May 1979.

Received October 1, 1979.




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Copyright © 1981 by The Endocrine Society