Endocrinology and Metabolism

Chronic ethanol feeding impairs endothelin-1-stimulated glucose uptake via decreased Gα11 expression in rat adipocytes

Nadia Rachdaoui, Becky M. Sebastian, Laura E. Nagy


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 Gα11 in plasma membranes, with no change in Gαq quantity. Activation of proline-rich tyrosine kinase 2 (PYK2), a downstream target of Gαq/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 Gα11 coupled to impaired endothelin-1-dependent activation of PYK2 contributes to this response.

  • glucose transporter-4
  • insulin
  • G proteins
  • proline-rich tyrosine kinase 2
  • p38 mitogen-activated protein kinase
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