title: Augmented Rac1 Expression and Activity are Associated with Oxidative Stress and Decline of β Cell Function in Obesity.
abstract: BACKGROUND
  The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and β cell dysfunction in obesity.
  
  
  METHODS
  In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 β cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed.
  
  
  RESULTS
  ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 β cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in β cells.
  
  
  CONCLUSIONS
  Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with β cell dysfunction through ROS production.
authors.affiliation: Peking University Fifth School of Clinical Medicine, Beijing Hospital, Beijing, China.
authors.forename: Shutong
authors.initials: S
authors.lastname: Zhou
authors.forename: Dongni
authors.initials: D
authors.lastname: Yu
authors.forename: Shangyong
authors.initials: S
authors.lastname: Ning
authors.forename: Heli
authors.initials: H
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Lei
authors.initials: L
authors.lastname: He
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Sun
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D006949:Hyperlipidemias / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D007328:Insulin; C487513:NSC 23766; D009479:Neuropeptides; D011743:Pyrimidines; D012333:RNA, Messenger; C484602:Rac1 protein, mouse; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein