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Title: Mechanisms of insulin resistance in cultured fibroblasts from a patient with leprechaunism: impaired post-binding actions of insulin and multiplication-stimulating activity. Author: Craig JW, Larner J, Locker EF, Widom B, Elders MJ. Journal: Metabolism; 1984 Dec; 33(12):1084-96. PubMed ID: 6094962. Abstract: The binding and action of insulin and of the insulin-like growth factor, multiplication-stimulating activity (MSA), were studied in cultured skin fibroblasts from an infant with leprechaunism and associated insulin resistance. Three actions of insulin were reduced in the leprechaun cells: activation of glycogen synthase was 30% as great as in control fibroblasts, the increase in 2-deoxyglucose transport was 33% of the control value, and the uptake of alpha-aminoisobutyric acid was sevenfold less sensitive to enhancement. On a molar basis, MSA was at least as effective as insulin in activating glycogen synthase in control fibroblasts; in the patient's cells there was a reduction in activation that paralleled the changes observed with insulin. To localize the site of insulin resistance, the binding of both [125I]-insulin and [125I]-MSA to fibroblasts was measured and found to be reduced in the leprechaun cells. However, the impairment of the actions of insulin and MSA in the patient's cells was not explained solely by the diminished binding of the two polypeptides. Since the hexose transport system and the terminal enzymes studied thus far are intact, the defect is postulated to involve the post-binding coupling mechanism and mediator formation.[Abstract] [Full Text] [Related] [New Search]