摘要：

Tumor necrosis factor-α (TNF-α) is a potent inducer of insulin resistance, and increased TNF-α expression is associated with impaired glucose disposal. Although insulin is the primary regulator of glucose transport in adipose, endothelin-1, a vasoconstrictor peptide that signals through the heterotrimeric G proteins Gα[sub q/11], potently stimulates glucose uptake in 3T3-L1 adipocytes by a mechanism independent of phosphatidylinositol (PI) 3-kinase. Here, we report that exposure of 3T3-L1 adipocytes to TNF-α for 48 h dose-dependently decreased endothelin-l-stimulated glucose uptake and translocation of GLUT4 to the plasma membrane. TNF-α exposure had no effect on endothelin-1 receptor number at the cell surface. In contrast, TNF-α treatment reduced the quantity of Gα[sub q/11] and proline-rich tyrosine kinase 2 (PYK2) and decreased endothelin-1-stimulated PYK2-Tyr[sup 402] tyrosine phosphorylation. Taken together, these results suggest that TNF-α-induced desensitization of endothelin-1-stimulated GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes is due, at least in part, to a decreased expression of Gα[sub q/11], leading to a suppression in tyrosine phosphorylation of PYK2.

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