Chronic ethanol feeding impairs endothelin-1-stimulated glucose uptake via decreased G alpha 11 expression in rat adipocytes.
Chronic ethanol feeding decreases insulin-stimulated glucose uptake in rat adipocytes. Here, we show that chronic ethanol also decreases endothelin-stimulated glucose uptake. Endothelin-1 increased uptake of 2-deoxyglucose 2.4-fold in adipocytes isolated from pair-fed rats. However, in adipocytes isolated from rats that had consumed a diet containing 35% ethanol for 4 wk, endothelin-1 did not increase glucose uptake. Although endothelin-1 increased GLUT4 quantity at the plasma membrane in adipocytes from pair-fed rats, there was no increase in GLUT4 after chronic ethanol feeding. Loss of endothelin-1-stimulated glucose uptake after ethanol feeding was associated with a specific decrease in the quantity of Galpha11 in plasma membranes, with no change in Galphaq quantity. Activation of proline-rich tyrosine kinase 2 (PYK2), a downstream target of Galphaq/11 that is required for endothelin-1-stimulated GLUT4 translocation in 3T3-L1 adipocytes, was also suppressed after chronic ethanol feeding. In contrast, activation of p38 MAPK by endothelin-1 was not affected by chronic ethanol exposure. These data demonstrate that chronic ethanol feeding suppresses endothelin-1-stimulated glucose uptake and suggest that decreased expression of Galpha11 coupled to impaired endothelin-1-dependent activation of PYK2 contributes to this response.
Rachdaoui
Nadia
N
Dept. of Nutrition, Case Western Reserve University, 2123 Abington Rd., Rm. 201, Cleveland, OH 44106-4906, USA.
Sebastian
Becky M
BM
Nagy
Laura E
LE
D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D003847:Deoxyglucose / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000008:administration & dosage*; D051418:Focal Adhesion Kinase 2; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D020962:Heterotrimeric GTP-Binding Proteins / Q000032:analysis*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases
D019332:Endothelin-1; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D000431:Ethanol; D003847:Deoxyglucose; D011505:Protein-Tyrosine Kinases; D051418:Focal Adhesion Kinase 2; C496054:Ptk2b protein, rat; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose