Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Biochem Biophys Res Commun. 2013 Nov 8;441(1):133-8. doi: 10.1016/j.bbrc.2013.10.026. Epub 2013 Oct 12.
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.
内质网(ER)应激与糖尿病的发生发展有关。本研究旨在探讨胰高血糖素样肽-1 类似物利拉鲁肽对β细胞 ER 应激的影响。结果发现,利拉鲁肽可通过抑制 PERK 和 IRE1 通路,减轻胰高血糖素样肽-1 类似物对 thapsigargin 诱导的 ER 应激和 ER 应激相关细胞凋亡的作用。进一步在 ER 应激诱导的 1 型糖尿病模型 Akita 小鼠中检测了利拉鲁肽的作用。给予利拉鲁肽治疗 8 周后,Akita 小鼠胰腺中 p-eIF2α 和 p-JNK 的水平明显降低,而对 INS 细胞胰岛素水平无显著影响。综上所述,本研究结果表明,利拉鲁肽可能通过减轻 ER 应激及其相关的细胞死亡来保护胰腺细胞。