Familial insulin-resistant diabetes secondary to an affinity defect of the insulin receptor.
We describe three siblings with a mild diabetes mellitus in combination with acanthosis nigricans and multiple minor physical abnormalities. Fasting plasma insulin was elevated up to 100-fold as compared with normal values, and the diabetes was classified as insulin resistant. Insulin-binding studies on erythrocytes, monocytes, and cultured fibroblasts disclosed an abnormally reduced binding capacity, as compared with that of healthy controls, which was most prominent at low concentrations of insulin. Scatchard analysis on erythrocytes of the three patients revealed a normal number of total insulin-binding sites per cell, but a complete lack of insulin binding to the high-affinity receptor component. The findings are consistent with the assumption of two genetically distinct types of insulin receptors.
D000052:Acanthosis Nigricans / Q000235:genetics; D000293:Adolescent; D000328:Adult; D001665:Binding Sites; D003920:Diabetes Mellitus / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D009000:Monocytes / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics*
D007328:Insulin; D011972:Receptor, Insulin