title: Crocetin attenuates palmitate-induced insulin insensitivity and disordered tumor necrosis factor-alpha and adiponectin expression in rat adipocytes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Xi
authors.forename: Z
authors.initials: Z
authors.lastname: Qian
authors.forename: G
authors.initials: G
authors.lastname: Xu
authors.forename: C
authors.initials: C
authors.lastname: Zhou
authors.forename: S
authors.initials: S
authors.lastname: Sun
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D052242:Adiponectin / Q000096:biosynthesis*; D000818:Animals; D000963:Antimetabolites; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D003847:Deoxyglucose; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis; D007333:Insulin Resistance; D008297:Male; D009861:Onium Compounds / Q000494:pharmacology; D010168:Palmitates / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014801:Vitamin A / Q000031:analogs & derivatives
chemical_list: D052242:Adiponectin; D000963:Antimetabolites; D000975:Antioxidants; D051275:Glucose Transporter Type 4; D009861:Onium Compounds; D010168:Palmitates; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C487773:trans-sodium crocetinate; D014801:Vitamin A; D002338:Carotenoids; C007517:diphenyleneiodonium; D003847:Deoxyglucose; D005947:Glucose; D000111:Acetylcysteine