| 17471172 |
Xi L, Qian Z, Xu G, Zhou C, Sun S: Crocetin attenuates palmitate-induced insulin insensitivity and disordered tumor necrosis factor-alpha and adiponectin expression in rat adipocytes. Br J Pharmacol. 2007 Jul;151(5):610-7. Epub 2007 Apr 30.
BACKGROUND AND PURPOSE: A number of studies have implicated adipocyte-derived factors in the development of insulin resistance. Intracellular redox status has been reported to play a significant role in the modulation of insulin action. This study was designed to investigate the potential of crocetin, a potent antioxidant, to protect adipocytes against the induction of insulin insensitivity and disordered expression of tumor necrosis factor (TNF)-alpha and adiponectin in vitro. EXPERIMENTAL APPROACH: We used palmitate to induce insulin resistance in freshly isolated rat adipocytes, and observed the effect of crocetin, N-acetylcysteine, diphenyleneiodonium, rotenone and oxypurinol. Insulin sensitivity was measured using 2-deoxy-D-[1-(3) H]-glucose uptake assay. Levels of glucose transporter 4, TNF-alpha and adiponectin were evaluated by immunoblot analysis, and levels of mRNA for TNF-alpha and adiponectin by reverse transcription-polymerase chain reaction analysis. Intracellular production of reactive oxygen species (ROS) was determined spectrofluorometrically using 2',7'-dichlorofluorescin diacetate. KEY RESULTS: Palmitate induced a 45% decrease in insulin-stimulated glucose uptake in adipocytes. The mRNA and protein expression of TNF-alpha were enhanced by 64% and 59% respectively whereas the mRNA and protein expression of adiponectin were reduced by 43% and 36% respectively by palmitate treatment. These changes were accompanied by a 54% increase in intracellular ROS levels. Crocetin, N-acetylcysteine and diphenyleneiodonium were found to attenuate these abnormalities. CONCLUSIONS AND IMPLICATIONS: Crocetin blocked the impaired insulin-stimulated glucose uptake and disordered TNF-alpha and adiponectin expression induced by palmitate in rat adipocytes. Inactivation of NADPH oxidase may account for these observations. |
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