title: GLP-1 analogue, Liraglutide protects human umbilical vein endothelial cells against high glucose induced endoplasmic reticulum stress.
abstract: OBJECTIVE
  Hyperglycemia induced endoplasmic reticulum (ER) stress in diabetic vascular cells is considered an increasingly important factor for the genesis and development of atherosclerosis and cardiovascular complications. This study investigated firstly, the effect of hyperglycemia in ER stress induction in Human Umbilical Vein Endothelial Cells (HUVECs) and secondly, the impact of Glucagon like petide-1 (GLP-1) analogue, Liraglutide, in reducing ER stress in HUVECs exposed to high glucose (HG).
  
  
  METHODS
  HUVECs were incubated for 12 hr in 5 mmol/L normal glucose (NG) or in 25 mmol/L (HG) glucose with or without different concentrations of Liraglutide (1 nM, 10 nM or 100 nM) and components of ER stress pathways studied, using western blotting, to assess their expression levels.
  
  
  RESULTS
  Our data confirmed that exposure of HUVECs to HG up-regulated both up- (Bip/Grp78, PERK and IRE1α) and downstream (Calnexin, PDI and Ero1-Lα) markers of ER stress compared with control. Furthermore, Liraglutide showed a dose dependent capacity in preventing the onset of ER stress in HUVECs, with a maximum activity at 100 nM. HG also upregulated proapoptotic PUMA protein levels compared to controls. Interestingly, Liraglutide also induced OPA1, a marker of mitochondrial fusion, in a dose dependent manner.
  
  
  CONCLUSIONS
  Liraglutide prevented the onset of ER stress in human endothelial cells exposed to HG. Our data suggest that Liraglutide may exert its effects by inducing mitochondrial fusion processes, thus preventing HG induced mitochondrial fragmentation and apoptosis in human endothelial cells.
authors: CSRL, University of Warwick, Warwick Medical School, University Hospital, Coventry, United Kingdom.
authors: Bruno
authors: B
authors: Schisano
authors: Alison L
authors: AL
authors: Harte
authors: Konstantinos
authors: K
authors: Lois
authors: Ponnusamy
authors: P
authors: Saravanan
authors: Nasser
authors: N
authors: Al-Daghri
authors: Omar
authors: O
authors: Al-Attas
authors: Lotte B
authors: LB
authors: Knudsen
authors: Philip G
authors: PG
authors: McTernan
authors: Antonio
authors: A
authors: Ceriello
authors: Gyanendra
authors: G
authors: Tripathi
mesh_terms: D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D000069450:Liraglutide
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D005947:Glucose