Decreased insulin binding in cultured lymphocytes from two patients with extreme insulin resistance.
[125I]Insulin binding has been studied in two patients with extreme insulin resistance using cultured B-lymphocytes transformed with Epstein-Barr virus. A cell line from a female infant with leprechaunism had insulin binding which was decreased 90% below the lower limit of normal. Lymphocytes from a young woman with type A extreme insulin resistance (associated with acanthosis nigricans and virilization) had insulin binding which was 80% depressed. In both cases, the defect in binding resulted from a decrease in the number of receptors per cell. The remaining receptors had normal properties, including a normal affinity for insulin and a normal specificity for insulin analogs. Insulin binding in cultured lymphocytes from these two insulin-resistant patients was also inhibited normally by antibodies to the insulin receptor. Immunological assays using anti-receptor antibodies confirmed the conclusion that the number of receptors was decreased. Affinity labeling of the leprechaun insulin receptor with [125I]insulin demonstrated the existence of an alpha-subunit with apparently normal molecular weight (130,000 daltons). However, the number of receptor molecules per cell appeared reduced.
D000293:Adolescent; D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000097:blood; D004392:Dwarfism / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011972:Receptor, Insulin / Q000097:blood / Q000276:immunology; D013577:Syndrome; D013997:Time Factors
D007328:Insulin; D011972:Receptor, Insulin