Dexamethasone inhibits insulin-stimulated recruitment of GLUt4 to the cell surface in rat skeletal muscle

• Published in: Metabolism, clinical and experimental clinical and experimental, 1998, Vol.47 (1), p.3-6
• Main Authors: Weinstein, Steven P., Wilson, Cindy M., Pritsker, Alla, Cushman, Samuel W.
• Format: Article
• Language: English
• Subjects: Animals; Azides - metabolism; Biological and medical sciences; Biological Transport; Body Weight - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; Deoxyglucose - pharmacokinetics; Dexamethasone - pharmacology; Disaccharides - metabolism; Glucose - metabolism; Glucose Transporter Type 4; Glycosides; Hormones. Endocrine system; Immunoblotting; Insulin - pharmacology; Male; Medical sciences; Monosaccharide Transport Proteins - metabolism; Muscle Proteins; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Pharmacology. Drug treatments; Photoaffinity Labels - metabolism; Precipitin Tests; Propylamines; Rats; Rats, Sprague-Dawley
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/S0026-0495(98)90184-6

To test the hypothesis that glucocorticoids reduce insulin-stimulated skeletal muscle glucose transport by inhibiting the recruitment of GLUT4 glucose transporters to the cell surface, we determined the effect of glucocorticoid treatment on cell-surface GLUT4 using the impermeant glucose transporter photolabel, 2- N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-[2- 3 H]1,3-bis-( d-mannos-4-yloxy)-2-propylamine (ATB-[2- 3H]BMPA), and GLUT4 immunoprecipitation. Male Sprague-Dawley rats were treated with dexamethasone ([Dex] 0.9 mg/kg for 2 days) and compared against pair-fed controls. 2-[ 3H]deoxyglucose (2-[ 3H]DG) uptake in isolated soleus muscles was measured under conditions in which uptake reflects glucose transport activity. In control muscles, 2-[ 3H]DG uptake was stimulated eightfold by insulin (20 nmol/L). Dex treatement reduced maximal insulin-stimulated 2-[ 3H]DG uptake by 48% ± 4% (mean ± SEM) and decreased cell-surface (ATB-[2- 3H]BMPA—photolabeled) GLUT4 by 48% ± 3%, despite an increase in total muscle GLUT4 content of 26% ± 7%. These findings indicate that glucocorticoid-induced inhibition of insulin-stimulated glucose transport in muscle is due to impaired recruitment of GLUT4 to the cell surface.