Chronic ethanol feeding impairs endothelin-1-stimulated glucose uptake via decreased G 11 expression in rat adipocytes

Rachdaoui, Nadia, Becky M. Sebastian, and Laura E. Nagy. Chronic ethanol feeding impairs endothelin-1-stimulated glucose uptake via decreased G 11 expression in rat adipocytes. Am J Physiol Endocrinol Metab 285: E303–E310, 2003. First published April 8, 2003; 10.1152/ajpendo. 00547.2002.—Chronic ethanol feeding decreases insulinstimulated 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 G 11 in plasma membranes, with no change in G q quantity. Activation of proline-rich tyrosine kinase 2 (PYK2), a downstream target of G q/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 G 11 coupled to impaired endothelin1-dependent activation of PYK2 contributes to this response.