We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-solubilized extracts. The monoclonal antibody to the IGF-I receptor (α-IR3) inhibits 125I-IGF-I binding and immunoprecipitates the IGF-I receptor. In addition, the α-subunit of IGF-I receptor is ∼10,000 Mr larger than the α-subunit of insulin receptor, and IGF-I stimulates phosphorylation of the β-subunit of the IGF-I receptor. IGF-I stimulates basal glucose transport in human adipocytes, but the concentrations of IGF-I required for half-maximal and maximal stimulation of glucose transport are 800- and 1000-fold greater than that of insulin. The possibility of IGF-I stimulating glucose transport by interacting predominantly with insulin receptors is suggested by data showing that 1) IGF-I competes with insulin-binding sites, 2) there is a lack of an additive effect with IGF-I and insulin in stimulating glucose transport, 3) α-IR3, which specifically inhibits IGF-I binding, does not inhibit IGF-I or insulin-stimulated glucose transport, 4) insulinreceptor antibody MA-10 inhibits IGF-I and insulinstimulated glucose transport, and 5) IGF-I stimulates insulin-receptor autophosphorylation, although its effect is markedly decreased compared with insulin. In summary, human adipocytes possess specific IGF-I receptors. However, IGF-I stimulates glucose transport predominantly by interacting with the insulin receptor.
Mechanism of IGF-I-Stimulated Glucose Transport in Human Adipocytes: Demonstration of Specific IGF-I Receptors Not Involved in Stimulation of Glucose Transport
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Madhur K Sinha, Cresada Buchanan, Nancy Leggett, Lourdes Martin, Prabhaker G Khazanie, Richard Dimarchi, Walter J Pories, José F Caro; Mechanism of IGF-I-Stimulated Glucose Transport in Human Adipocytes: Demonstration of Specific IGF-I Receptors Not Involved in Stimulation of Glucose Transport. Diabetes 1 October 1989; 38 (10): 1217–1225. https://doi.org/10.2337/diab.38.10.1217
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