title: Asymmetric dimethylarginine impairs glucose utilization via ROS/TLR4 pathway in adipocytes: an effect prevented by vitamin E.
abstract: BACKGROUND
  Asymmetric dimethylarginine (ADMA), the inhibitor of nitric oxide synthase (NOS), has been reported to be associated with glucose metabolism, but its mechanisms remain unknown.
  
  
  METHODS
  In 3T3-L1 adipocytes, we measured the effects of ADMA on glucose transport process under basal or insulin-induced condition, and examined the production of nitric oxide (NO), reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-alpha), and the expression of toll-like receptor 4 (TLR4).
  
  
  RESULTS
  ADMA significantly impaired basal or insulin-stimulated 2-deoxy- [3H] glucose uptake, and decreased the expression of insulin receptor substrate-1 (IRS-1) and glucose transporter-4 (GLUT4). Phosphorylated protein of IRS-1 and translocation of GLUT4 with insulin-stimulation were also inhibited by ADMA. NO decreased, while production of ROS and TNF-alpha, and expression of TLR4 increased after ADMA treatment. Vitamin E reduced the effects of ADMA on glucose transport system, and on NO, ROS and TLR4. Moreover, vitamin E decreased ADMA contents by up-regulating dimethylarginine dimethylaminohydrolase (DDAH) activity in adipocytes. Though L-arginine also increased NO level, but failed to reduce the effects of ADMA.
  
  
  CONCLUSIONS
  ADMA significantly impairs both basal and insulin-stimulated glucose transport in adipocytes, which may relate to activation of the ROS/TLR4 pathway.
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, China.
authors: Zhi-Chun
authors: ZC
authors: Yang
authors: Kuan-Song
authors: KS
authors: Wang
authors: Yan
authors: Y
authors: Wu
authors: Xiao-Qing
authors: XQ
authors: Zou
authors: Yue-Yun
authors: YY
authors: Xiang
authors: Xiao-Ping
authors: XP
authors: Chen
authors: Yuan-Jian
authors: YJ
authors: Li
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D005947:Glucose