Mechanism of IGF-I-Stimulated Glucose Transport in Human Adipocytes: Demonstration of Specific IGF-I Receptors Not Involved in Stimulation of Glucose Transport
- Madhur K Sinha,
- Cresada Buchanan,
- Nancy Leggett,
- Lourdes Martin,
- Prabhaker G Khazanie,
- Richard Dimarchi,
- Walter J Pories and
- José F Caro
- Departments of Medicine, Clinical Pathology, and Surgery, East Carolina University School of Medicine Greenville, North Carolina Eli Lilly and Company Indianapolis, Indiana
- 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.
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.
- Copyright © 1989 by the American Diabetes Association