title: 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.
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Zhao
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Anlin
authors.initials: A
authors.lastname: Peng
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D000069450:Liraglutide; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; C000717248:Hspa5 protein, mouse; D019284:Thapsigargin; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D048031:JNK Mitogen-Activated Protein Kinases
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