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Crocetin attenuates palmitate‐induced insulin insensitivity and disordered tumor necrosis factor‐ α and adiponectin expression in rat adipocytes
Author(s) -
Xi L,
Qian Z,
Xu G,
Zhou C,
Sun S
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707276
Subject(s) - adiponectin , insulin resistance , medicine , endocrinology , crocetin , adipocyte , insulin , glucose transporter , intracellular , chemistry , glucose uptake , tumor necrosis factor alpha , biology , biochemistry , adipose tissue , carotenoid
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)‐α 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‐α and adiponectin were evaluated by immunoblot analysis, and levels of mRNA for TNF‐α 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‐α 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‐α and adiponectin expression induced by palmitate in rat adipocytes. Inactivation of NADPH oxidase may account for these observations. British Journal of Pharmacology (2007) 151 , 610–617; doi: 10.1038/sj.bjp.0707276