Ethanol stimulates glucose uptake and translocation of GLUT-4 in H9c2 myotubes via a Ca(2+)-dependent mechanism.
Short-term exposure to ethanol impairs glucose homeostasis, but the effects of ethanol on individual components of the glucose disposal pathway are not known. To understand the mechanisms by which ethanol disrupts glucose homeostasis, we have investigated the direct effects of ethanol on glucose uptake and translocation of GLUT-4 in H9c2 myotubes. Short-term treatment with 12.5-50 mM ethanol increased uptake of 2-deoxyglucose by 1.8-fold in differentiated myotubes. Pretreatment of H9c2 myotubes with 100 nM wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had no effect on ethanol-induced increases in 2-deoxyglucose uptake. In contrast, preincubation with 25 microM dantrolene, an inhibitor of Ca(2+) release from the sarcoplasmic reticulum, blocked the stimulation of 2-deoxyglucose uptake by ethanol. Increased 2-deoxyglucose uptake after ethanol treatment was associated with a decrease in small intracellular GLUT-4 vesicles and an increase in GLUT-4 localized at the cell surface. In contrast, ethanol had no effect on the quantity of GLUT-1 and GLUT-3 at the plasma membrane. These data demonstrate that physiologically relevant concentrations of ethanol disrupt the trafficking of GLUT-4 in H9c2 myotubes resulting in translocation of GLUT-4 to the plasma membrane and increased glucose uptake.
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Department of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Schroeder
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Nagy
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D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D003620:Dantrolene / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000493:pharmacokinetics*; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000201:enzymology*; D009124:Muscle Proteins; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D000077191:Wortmannin
D000730:Androstadienes; D000963:Antimetabolites; D002118:Calcium; D002492:Central Nervous System Depressants; D003620:Dantrolene; D003847:Deoxyglucose; D004791:Enzyme Inhibitors; D000431:Ethanol; D005947:Glucose; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009125:Muscle Relaxants, Central; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; C495694:Slc2a4 protein, rat