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-[2-3H]1,3-bis-(D-mann os-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 treatment 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.
Weinstein
S P
SP
Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA.
Wilson
C M
CM
Pritsker
A
A
Cushman
S W
SW
D000818:Animals; D001386:Azides / Q000378:metabolism; D001692:Biological Transport; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000494:pharmacology*; D004187:Disaccharides / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006027:Glycosides; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D019920:Photoaffinity Labels / Q000378:metabolism; D011233:Precipitin Tests; D011437:Propylamines; D051381:Rats; D017207:Rats, Sprague-Dawley
D001386:Azides; D004187:Disaccharides; D051275:Glucose Transporter Type 4; D006027:Glycosides; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D019920:Photoaffinity Labels; D011437:Propylamines; C495694:Slc2a4 protein, rat; C065412:2-N-(4-(1-azitrifluoroethyl)benzoyl)-1,3-bis-(mannos-4-yloxy)-2-propylamine; D003907:Dexamethasone; D003847:Deoxyglucose; D005947:Glucose