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Cultured lymphocytes transformed by Epstein--Barr virus were employed to study insulin receptors from a patient with extreme insulin resistance associated with the syndrome of leprechaunism. With cultured lymphocytes from normal subjects, insulin binding to its receptor is exquisitely sensitive to changes in temperature and pH. In cells from normal subjects, insulin binding was increased by approximately 250% as the temperature was decreased from 37 degrees C to 12 degrees C. In contrast, with cells from the leprechaun, insulin binding was only approximately 30% higher at 12 degrees C than at 37 degrees C. Similarly, insulin binding to cells from the leprechaun was markedly less sensitive to changes in pH, as compared to cells from normal subjects. Binding studies suggested that the number of insulin receptors per cell was within the normal range in this patient. Despite the unusual characteristics of insulin binding in cells from this insulin-resistant patient, the receptors were typical in at least two respects: (i) binding was inhibited normally by antibodies to the receptor; and (ii) the specificity for insulin analogs was normal (chicken insulin greater than porcine insulin much greater than guinea pig insulin greater than porcine proinsulin). This patient has an inborn error affecting insulin receptor function. The receptor's binding function was abnormal in having decreased sensitivity to alterations in temperature and pH. However, the level of insulin binding to cells from the leprechaun was within normal limits. Consequently, the hormonal resistance probably results from a decreased ability of the receptor to couple insulin binding to insulin action.

Qualitative abnormalities in insulin binding in a patient with extreme insulin resistance: decreased sensitivity to alterations in temperature and pH.