Schisano, Bruno, Harte, Alison L., Lois, Konstantinos, Saravanan, Ponnusamy, Al-Daghri, Nasser, Al-Attas, Omar S., Knudsen, Lotte B., McTernan, Philip G., Ceriello, Antonio and Tripathi, Gyanendra. (2012) GLP-1 analogue, Liraglutide protects human umbilical vein endothelial cells against high glucose induced endoplasmic reticulum stress. Regulatory Peptides, Vol.174 (No.1-3). pp. 46-52. ISSN 01670115

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Abstract

Background and purpose 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). Experimental approach 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. Key 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 and implications 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.

Item Type:	Journal Article
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Regulatory Peptides
Publisher:	Elsevier BV
ISSN:	01670115
Date:	10 February 2012
Volume:	Vol.174
Number:	No.1-3
Page Range:	pp. 46-52
Identification Number:	10.1016/j.regpep.2011.11.008
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/43598

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