Liraglutide Inhibits Endoplasmic Reticulum Stress in Pancreatic Beta Cells via Regulation of the Homeodomain Transcription Factor Nkx6.1

Abstract

The GLP-1 mitigates the endoplasmic reticulum (ER) stress in β cells. Nkx6.1 plays an important role in the development and survival of β cells. This study aims to investigate the relation of Nkx6.1 and liraglutide in the protection effect of endoplasmic reticulum stress in INS-1-3 cells. INS-1-3 cells were divided into different groups for treatment: control group, thapsigargin (TG)-treated group, TG and GLP-1 co-treated group. Knockdown of Nkx6.1 was established by lentivirus infection. RT-PCR was used to verify the expression changes of target genes. MTT and flow cytometry analysis were used to detect cell viability and apoptosis rates. Glucose stimulates insulin secretion (GSIS) was used to measure β cell function. In TG-treated cells, liraglutide significantly increased cell viability and GSIS by 1.53 and 1.89 folds. These were associated with the suppression of the PERK, IRE1 and ATF-6 pathways. Knock down of Nkx6.1 partially diminished protective effect of liraglutide. The cell viability and GSIS were decreased by 24.7% and 54.0%. And both of the early and late apoptosis were increased by 1.55, 1.10 folds. Liraglutide protected INS-1-3 cells from TG-induced ER stress by suppressing the PERK, IRE1 and ATF-6 pathways. And its protective effects on ER stress was partially via transcription factor Nkx6.1. Disclosure Y. Li: None. Y. Dong: None. L. Shilun: None. P. Xue: None.