GLP-1 analogue, Liraglutide protects human umbilical vein endothelial cells against high glucose induced endoplasmic reticulum stress

Bruno Schisano, Alison L. Harte, Konstantinos Lois, Ponnusamy Saravanan, Nasser Al-Daghri, Omar Al-Attas, Lotte B. Knudsen, Philip G. McTernan, Antonio Ceriello, Gyanendra Tripathi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)46-52
Number of pages7
JournalRegulatory Peptides
Volume174
Issue number1-3
DOIs
Publication statusPublished - Feb 10 2012

Keywords

  • ER stress
  • GLP-1
  • HUVEC
  • Liraglutide

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience

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