Diabetes, Vol 41, Issue 6 728-735, Copyright © 1992 by American Diabetes Association

ARTICLES

Role of glucose transporters in glucocorticoid-induced insulin resistance. GLUT4 isoform in rat skeletal muscle is not decreased by dexamethasone

RS Haber and SP Weinstein
Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.

The diabetogenic effects of glucocorticoid excess are due in part to peripheral resistance to insulin. To test the hypothesis that glucocorticoid-induced peripheral insulin resistance might be attributable to a decreased number of glucose transporters, we examined the effects of dexamethasone treatment on the expression of the GLUT4 (insulin regulatable) glucose transporter in skeletal muscle, the major site of insulin-mediated glucose uptake. Dexamethasone treatment of rats (1 mg/day for 1 wk) induced hyperglycemia and hyperinsulinemia. At dosages of either 0.1 or 1 mg/day, insulin-stimulated 2-deoxyglucose uptake in isolated soleus muscle was reduced by greater than or equal to 50%, demonstrating the presence of insulin resistance in skeletal muscle. Immunoblots of crude membranes from deep quadriceps muscle showed that dexamethasone treatment (1 mg/day) increased the amount of GLUT4 protein by 84%. GLUT4 mRNA abundance was similarly increased when expressed per unit RNA but was unchanged when expressed on a DNA basis because the tissue RNA content was decreased by dexamethasone. In contrast to quadriceps, GLUT4 protein concentration in soleus and extensor digitorum longus extracts was not significantly increased by dexamethasone treatment. Because glucocorticoids cause selective atrophy of type IIb muscle fibers, which express relatively less GLUT4 protein, the apparent increase in GLUT4 content in quadriceps muscle from dexamethasone-treated animals may have resulted from inadvertent increased sampling of GLUT4-enriched type I and IIA fibers, caused by a glucocorticoid-induced decrease in the relative mass of the GLUT4-poor type IIb fibers. We conclude that glucocorticoids do not decrease GLUT4 content in skeletal muscle and that glucocorticoid-induced insulin resistance in this tissue is not due to suppression of glucose transporter gene expression.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Qi and B. Rodrigues Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E654 - E667. [Abstract] [Full Text] [PDF]

				S. B. Choi, J. S. Jang, S. M. Hong, D. W. Jun, and S. Park Exercise and dexamethasone oppositely modulate {beta}-cell function and survival via independent pathways in 90% pancreatectomized rats. J. Endocrinol., August 1, 2006; 190(2): 471 - 482. [Abstract] [Full Text] [PDF]

				C. Corporeau, C. L. Foll, M. Taouis, J.-P. Gouygou, J.-P. Berge, and J. Delarue Adipose tissue compensates for defect of phosphatidylinositol 3'-kinase induced in liver and muscle by dietary fish oil in fed rats Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E78 - E86. [Abstract] [Full Text] [PDF]

				S. M. Willi, A. Kennedy, P. Wallace, E. Ganaway, N. L. Rogers, and W. T. Garvey Troglitazone Antagonizes Metabolic Effects of Glucocorticoids in Humans: Effects on Glucose Tolerance, Insulin Sensitivity, Suppression of Free Fatty Acids, and Leptin Diabetes, October 1, 2002; 51(10): 2895 - 2902. [Abstract] [Full Text] [PDF]

				C. Severino, P. Brizzi, A. Solinas, G. Secchi, M. Maioli, and G. Tonolo Low-dose dexamethasone in the rat: a model to study insulin resistance Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E367 - E373. [Abstract] [Full Text] [PDF]

				H. Morita, Y. Oki, T. Ito, H. Ohishi, S. Suzuki, and H. Nakamura Administration of Troglitazone, but Not Pioglitazone, Reduces Insulin Resistance Caused by Short-Term Dexamethasone (DXM) Treatment by Accelerating the Metabolism of DXM Diabetes Care, April 1, 2001; 24(4): 788 - 789. [Full Text]

				T. Hahn, S. Barth, R. Graf, M. Engelmann, D. Beslagic, J. M. H. M. Reul, F. Holsboer, G. Dohr, and G. Desoye Placental Glucose Transporter Expression Is Regulated by Glucocorticoids J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1445 - 1452. [Abstract] [Full Text]

				P. Schneiter and L. Tappy Kinetics of dexamethasone-induced alterations of glucose metabolism in healthy humans Am J Physiol Endocrinol Metab, November 1, 1998; 275(5): E806 - E813. [Abstract] [Full Text] [PDF]