title: A new oxovanadium complex enhances renal function by improving insulin signaling pathway in diabetic mice.
abstract: OBJECTIVE
  Since vanadium complexes have insulin-mimetic effects and can be used to treat complications of diabetes, we aimed to screen a new oxovanadium complex with a low toxicity, and investigate its insulin-mimetic effects, as well as the mechanism of improvement to diabetic mouse renal function.
  
  
  METHODS
  Cells were treated with oxovanadium complexes, and viability was assessed by MTT assay. Diabetic mouse model was established using alloxan. Blood urea nitrogen (BUN) and serum creatinine (SCr) in the mice were measured using an automatic biochemical analyzer, and blood glucose was measured using a Glucoval Compact meter. Expression of proteins related to the insulin signaling pathway in the renal cortex of mice was measured by Western blot analysis.
  
  
  RESULTS
  Diabetic mice developed high blood glucose, BUN and SCr levels compared with control mice. The new oxovanadium complex with 3,5-dimethyl-pyrazolyl ligand, VO(HB(3,5-Me2pz)3)(3,5-Me2pz)(SCN)(SCNH)2, showed low toxicity and significantly reduced blood glucose, BUN and SCr levels in the diabetic mice. Additionally, p42/p44MAPK and Akt phosphorylation was markedly increased in diabetic mice and was decreased by treatment with the new oxovanadium complex. Caveolin-1 (Cav-1) expression was greatly decreased in diabetic mice and significantly increased after treatment with the new oxovanadium complex.
  
  
  CONCLUSIONS
  The new oxovanadium complex, with 3,5-dimethyl-pyrazolyl ligand, improves kidney function in diabetic mice, and its mechanism may involve regulation of the insulin signaling pathway.
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian, China; School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian, China; Department of Anesthesiology, Emory University School of Medicine, GA, USA.
authors.forename: D D
authors.initials: DD
authors.lastname: Chen
authors.affiliation: Liaoning Key Lab of Biotechnology and Molecular Medicine R&D, Dalian, China; School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Xing
authors.affiliation: College of engineering, Swansea University, Swansea, UK.
authors.forename: N
authors.initials: N
authors.lastname: Ge
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Centre for Regenerative Medicine, First Affiliated Hospital of Dalian Medical, University, Dalian, China. Electronic address: liujing.dlrmc@hotmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Life Science, Liaoning Normal University, Dalian, China; Liaoning Key Lab of Biotechnology and Molecular Medicine R&D, Dalian, China. Electronic address: weizou60@hotmail.com.
authors.forename: W
authors.initials: W
authors.lastname: Zou
mesh_terms: D000496:Alloxan / Q000009:adverse effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001806:Blood Urea Nitrogen; D051242:Caveolin 1 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D007328:Insulin / Q000502:physiology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D014638:Vanadates / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D051242:Caveolin 1; D007328:Insulin; C075743:oxovanadium IV; D014638:Vanadates; D000496:Alloxan; D003404:Creatinine; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Caveolin-1; Diabetes; Diabetic nephropathy; Insulin signaling pathway; Oxovanadium complexes