Mechanism of IGF-I-Stimulated Glucose Transport in Human Adipocytes: Demonstration of Specific IGF-I Receptors Not Involved in Stimulation of Glucose Transport

  1. José F Caro
  1. Departments of Medicine, Clinical Pathology, and Surgery, East Carolina University School of Medicine Greenville, North Carolina Eli Lilly and Company Indianapolis, Indiana
  1. Address correspondence and reprint request to Dr. Madhur K. Sinha, Section of Endocrinology and Metabolism, Department of Medicine, ECU School of Medicine, Greenville, NC 27858-4354.

Abstract

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.

  • Received August 5, 1988.
  • Revision received May 16, 1989.
  • Accepted May 16, 1989.
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