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

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). HUVECs were incubated for 12hr in 5mmol/L normal glucose (NG) or in 25mmol/L (HG) glucose with or without different concentrations of Liraglutide (1nM, 10nM or 100nM) and components of ER stress pathways studied, using western blotting, to assess their expression levels. 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 100nM. 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. 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. ► Endoplasmic Reticulum (ER) stress is induced by high glucose in human umbilical vein endothelial cells (HUVECs). ► GLP-1 analogue liraglutide prevented the onset of ER stress in HUVECs exposed to high glucose. ► Liraglutide may exert its effects by inducing mitochondrial fusion via OPA1 activation.