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 ≥ 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.
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Original Articles|
June 01 1992
Role of Glucose Transporters in Glucocorticoid-Induced Insulin Resistance: GLUT4 Isoform in Rat Skeletal Muscle is Not Decreased by Dexamethasone
Richard S Haber;
Richard S Haber
Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place
New York, New York
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Steven P Weinstein
Steven P Weinstein
Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place
New York, New York
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Address correspondence and reprint requests to Dr. Richard S. Haber, Box 1055, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029.
Diabetes 1992;41(6):728–735
Article history
Received:
August 27 1991
Revision Received:
February 04 1992
Accepted:
February 04 1992
PubMed:
1587399
Citation
Richard S Haber, Steven P Weinstein; Role of Glucose Transporters in Glucocorticoid-Induced Insulin Resistance: GLUT4 Isoform in Rat Skeletal Muscle is Not Decreased by Dexamethasone. Diabetes 1 June 1992; 41 (6): 728–735. https://doi.org/10.2337/diab.41.6.728
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