دورية
Arachidonic Acid Stimulates Glucose Uptake in 3T3-L1 Adipocytes by Increasing GLUT1 and GLUT4 Levels at the Plasma Membrane
| العنوان: | Arachidonic Acid Stimulates Glucose Uptake in 3T3-L1 Adipocytes by Increasing GLUT1 and GLUT4 Levels at the Plasma Membrane |
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| المؤلفون: | Nugent, Claire, Prins, Johannes B., Whitehead, Jonathan P., Wentworth, John M., Chatterjee, V. Krishna K., O'Rahilly, Stephen |
| المصدر: | Journal of Biological Chemistry; March 2001, Vol. 276 Issue: 12 p9149-9157, 9p |
| مستخلص: | Exposure of insulin-sensitive tissues to free fatty acids can impair glucose disposal through inhibition of carbohydrate oxidation and glucose transport. However, certain fatty acids and their derivatives can also act as endogenous ligands for peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor that positively modulates insulin sensitivity. To clarify the effects of externally delivered fatty acids on glucose uptake in an insulin-responsive cell type, we systematically examined the effects of a range of fatty acids on glucose uptake in 3T3-L1 adipocytes. Of the fatty acids examined, arachidonic acid (AA) had the greatest positive effects, significantly increasing basal and insulin-stimulated glucose uptake by 1.8- and 2-fold, respectively, with effects being maximal at 4 h at which time membrane phospholipid content of AA was markedly increased. The effects of AA were sensitive to the inhibition of protein synthesis but were unrelated to changes in membrane fluidity. AA had no effect on total cellular levels of glucose transporters, but significantly increased levels of GLUT1 and GLUT4 at the plasma membrane. While the effects of AA were insensitive to cyclooxygenase inhibition, the lipoxygenase inhibitor, nordihydroguaiaretic acid, substantially blocked the AA effect on basal glucose uptake. Furthermore, adenoviral expression of a dominant-negative PPARγ mutant attenuated the AA potentiation of basal glucose uptake. Thus, AA potentiates basal and insulin-stimulated glucose uptake in 3T3-L1 adipocytes by a cyclooxygenase-independent mechanism that increases the levels of both GLUT1 and GLUT4 at the plasma membrane. These effects are at least partly dependent onde novoprotein synthesis, an intact lipoxygenase pathway and the activation of PPARγ with these pathways having a greater role in the absence than in the presence of insulin. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 00219258 1083351X |
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| DOI: | 10.1074/jbc.M009817200 |