Diabetes, Vol 38, Issue 10 1217-1225, Copyright © 1989 by American Diabetes Association

ARTICLES

Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport

MK Sinha, C Buchanan, N Leggett, L Martin, PG Khazanie, R Dimarchi, WJ Pories and JF Caro
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 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 (alpha-IR3) inhibits 125I-IGF-I binding and immunoprecipitates the IGF-I receptor. In addition, the alpha-subunit of IGF-I receptor is approximately 10,000 Mr larger than the alpha-subunit of insulin receptor, and IGF-I stimulates phosphorylation of the beta-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) alpha-IR3, which specifically inhibits IGF-I binding, does not inhibit IGF-I or insulin-stimulated glucose transport, 4) insulin-receptor antibody MA-10 inhibits IGF-I and insulin-stimulated 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.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. S. Shankar, R. V. Considine, J. C. Gorski, and H. O. Steinberg Insulin sensitivity is preserved despite disrupted endothelial function Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E691 - E696. [Abstract] [Full Text] [PDF]

				T. Pratipanawatr, W. Pratipanawatr, C. Rosen, R. Berria, M. Bajaj, K. Cusi, L. Mandarino, S. Kashyap, R. Belfort, and R. A. DeFronzo Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1360 - E1368. [Abstract] [Full Text] [PDF]

				H. I. Krieger-Brauer, P. K. Medda, and H. Kather Insulin-induced Activation of NADPH-dependent H2O2 Generation in Human Adipocyte Plasma Membranes Is Mediated by Galpha i2 J. Biol. Chem., April 11, 1997; 272(15): 10135 - 10143. [Abstract] [Full Text] [PDF]