title: Vav3, a GEF for RhoA, Plays a Critical Role under High Glucose Conditions.
abstract: BACKGROUND
  The role of small GTPase molecules is poorly understood under high glucose conditions.
  
  
  METHODS
  We analyzed the expression pattern of Vav3 in skeletal muscle C2C12 cells under high glucose culture condition with reverse transcription-polymerase chain reaction and Western blot analysis. We also measured glucose uptake using isotope-labelled glucose.
  
  
  RESULTS
  We showed that expression of Vav3 (a guanine nucleotide exchange factor for RhoA) increased. mRNA and protein levels in skeletal muscle C2C12 cells under high glucose conditions. The AMP-activated protein kinase (AMPK) activator AMPK agonist 5-aminoimidazole-4-carboxy-amide-1-d-ribofuranoside (AICAR) suppressed high glucose-induced Vav3 induction. In addition, exposure of cells to high glucose concentration increased the phosphorylation of PAK-1, a molecule downstream of RhoA. The phosphorylation of paxillin, a downstream molecule of PAK-1, was also increased by exposure to high glucose. Phosphorylation of these molecules was not observed in the presence of AICAR, indicating that AMPK is involved in the RhoA signal pathway under high glucose conditions. Knock down of Vav3 enhances metformin-mediated glucose uptake. Inhibition of AMPK blocked the increases of Vav3 knock down-induced glucose uptake. Metformin-mediated Glut4 translocation was also increased by Vav3 knock-down, suggesting that Vav3 is involved in metformin-mediated glucose uptake.
  
  
  CONCLUSIONS
  These results demonstrate that Vav3 is involved in the process of metformin-mediated glucose regulation.
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jie
authors.initials: J
authors.lastname: Sha
authors.affiliation: Bando Hospital, Korea.
authors.forename: Jungsik
authors.initials: J
authors.lastname: Na
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ji Hae
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Ji Wook
authors.initials: JW
authors.lastname: Moon
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
keywords: AMP-activated protein kinases; Diabetes; High glucose; Metformin; Vav3