Schisano, Bruno, Harte, Alison L., Lois, Konstantinos, Saravanan, Ponnusamy, Al-Daghri, Nasser M., Al-Attas, Omar S., Knudsen, Lotte B., McTernan, P. 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. doi:10.1016/j.regpep.2011.11.008 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 Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
| Journal or Publication Title: | Regulatory Peptides |
| Publisher: | Elsevier BV |
| ISSN: | 01670115 |
| Official Date: | 10 February 2012 |
| Dates: | Date Event 10 February 2012 Published |
| Volume: | Vol.174 |
| Number: | No.1-3 |
| Page Range: | pp. 46-52 |
| DOI: | 10.1016/j.regpep.2011.11.008 |
| Status: | Peer Reviewed |
| Publication Status: | Published |
| Access rights to Published version: | Restricted or Subscription Access |
| URI: | https://wrap.warwick.ac.uk/43598/ |
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