title: Resveratrol via activation of LKB1-AMPK signaling suppresses oxidative stress to prevent endothelial dysfunction in diabetic mice.
abstract: BACKGROUND
  Resveratrol, a phytoalexin, is reported to activate AMP-activated protein kinase (AMPK) in vascular cells. Whether resveratrol via activation of AMPK improves endothelial dysfunction in diabetes remains unknown. Here, we reported that activation of AMPK is required for resveratrol-induced improvement of endothelial function in diabetic mice.
  
  
  METHODS
  AMPK phosphorylation and activity, productions of reactive oxygen species, endothelium-dependent/independent relaxation were determined in vitro or in vivo.
  
  
  RESULTS
  Exposure of cultured human umbilical vein endothelial cells (HUVECs) to resveratrol activates AMPK by increasing the thr172 phosphorylation and its activities in time/dose-dependent manner. Loss function of liver kinase B1 by siRNA or mutant abolished resveratrol-induced AMPK activation. Incubation of endothelial cells with high glucose (HG) markedly induced oxidative stress of HUVECs, which was abolished by resveratrol in AMPK-dependent manner. In isolated mice aortas, resveratrol, AICAR or apocynin improved endothelium-dependent relaxation impaired by HG. In animal studies, streptozotocin-induced hyperglycemia dramatically increased oxidative stress and caused endothelial dysfunction, which were reversed by administration of resveratrol.
  
  
  CONCLUSIONS
  We conclude that AMPK activation is required for resveratrol to improve endothelial function in diabetic mice.
authors.affiliation: a Department of Biomedical Engineering , College of Engineering, Peking University , Beijing , China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: b Department of Orthopaedics , The Third Xiangya Hospital, Central South University , Changsha , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006943:Hyperglycemia / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D012265:Ribonucleotides / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D012265:Ribonucleotides; D013267:Stilbenes; D000620:Aminoimidazole Carboxamide; D012264:Ribonucleotide Reductases; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D000077185:Resveratrol
keywords: AMPK; diabetes; endothelial dysfunction; oxidative stress; resveratrol