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.