Dexamethasone inhibits insulin-stimulated recruitment of GLUT4 to the cell surface in rat skeletal muscle

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-H-3]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-[H-3]deoxyglucose (2-[H-3]DG) uptake in isolated soleus muscles was measured under conditions in which uptake reflects glucose transport activity. In control muscles, 2-[H-3]DG uptake was stimulated eightfold by insulin (20 nmol/L), Dex treatment reduced maximal insulin-stimulated 2-[H-3]DG uptake by 48% +/- 4% (mean +/- SEM) and decreased cell-surface (ATB-[2-H-3]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. Copyright (C) 1998 by W.B. Saunders Company.