Stimulation of glucose incorporation and amino acid transport by insulin and an insulin-like growth factor in fibroblasts with defective insulin receptors cultured from a patient with leprechaunism.

Publisher Website
Google Scholar
Abstract
Fibroblasts cultured from an infant with leprechaunism and insulin resistance exhibited a profound, selective defect in insulin binding. The effect of this defect on 2 acute metabolic actions of insulin thought to be mediated by the insulin receptor, glucose incorporation and N-methyl-.alpha.-aminoisobutyric acid (Me-AiBu) uptake was examined. In the patient''s fibroblasts, maximal insulin-stimulated glucose incorporation was < 25% of that in control fibroblasts, whereas stimulation by H2O2, an insulinomimetic agent that acts distal to the insulin receptor, was normal. Insulin stimulated Me-AiBu uptake to the same extent in patient''s and control fibroblasts. Impaired glucose incorporation and relatively normal Me-AiBu uptake also were observed in the patient''s cells with multiplication-stimulating activity, an insulin-like growth factor, despite the fact that multiplication-stimulating activity appeared to stimulate both responses in normal fibroblasts via an insulin-like growth factor receptor. The divergent effects on 2 hormone-stimulated functions in the patient''s cells suggest differences in the coupling of a receptor to different effectors. The same coupling mechanisms appear to be used by insulin receptors and receptors for insulin-like growth factors.