Effect of Liraglutide on endoplasmic reticulum stress in diabetes

Abstract

Endoplasmic reticulum (ER) stress is associated with the development of diabetes. The present study sought to investigate the effect of Liraglutide, a glucagon like peptide 1 analogue, on ER stress in β-cells. We found that Liraglutide protected the pancreatic INS-1 cells from thapsigargin-induced ER stress and the ER stress associated cell apoptosis, mainly by suppressing the PERK and IRE1 pathways. We further tested the effects of Liraglutide in the Akita mouse, an ER-stress induced type 1 diabetes model. After administration of Liraglutide for 8weeks, p-eIF2α and p-JNK were significantly decreased in the pancreas of the Akita mouse, while the treatment showed no significant impact on the levels of insulin of INS-cells. Taken together, our findings suggest that Liraglutide may protect pancreatic cells from ER stress and its related cell death.

Keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ATF-6; Akita mouse; Bip; C/EBP homologous protein; CHOP; Diabetes; ER; ER stress; GLP-1; INS-1 cells; IRE1; Liraglutide; MTT; PERK; TG; UPR; activating transcription factor 6; double-stranded RNA-activated protein kinase (PKR)-like ER kinase; eIF2α; endoplasmic reticulum; eukaryotic translation initiation factor 2α; glucagon-like peptide 1; inositol requiring enzyme 1; luminal binding protein (also known as GRP78); thapsigargin; unfolded protein response.