Jing Yin Jia, Bo Li Yan, Ming Cao Ming, Wang Yang
The Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Int J Endocrinol Metab. 2013 Summer;11(3):184-90. doi: 10.5812/ijem.8088. Epub 2013 Jul 1.
Type 2 diabetes mellitus (T2D) is a metabolic disease characterized by dysfunction of pancreatic beta cell and insulin resistance. Liraglutide, which has many special anti-diabetes biological effects, is found to inhibit beta cell death and ameliorate endoplasmic reticulum stress (ERs) induced by free fatty acid (FFA). Macroautophagy (hereafter referred to as autophagy) altered by FFA is also associated with the dysfunction or death of pancreatic beta cells.
We aim at proving that Liraglutide improves the survival of INS-1 cells by promoting autophagy.
Cell survival was assessed by CCK8 assay. The percentage of apoptotic cells was determined by flow cytometric assay after Annexin V-FITC/PI staining. Expression of LC3 was detected by western blotting. MDC staining and transmission electron microscopy (TEM) were used in the measurement of autophagy.
Apoptosis induced by PA in INS-1 cells was significantly resolved after Liraglutide treatment. Simultaneously, autophagy was enhanced with the treatment of PA and Liraglutide.
Liraglutide appears to protect INS-1 cells from apoptosis FFA-induced by promoting autophagy.
These findings provide a novel role for GLP-1 analogue in preventing or treating with T2D.
2型糖尿病(T2D)是一种以胰腺β细胞功能障碍和胰岛素抵抗为特征的代谢性疾病。利拉鲁肽具有许多特殊的抗糖尿病生物学效应,被发现可抑制β细胞死亡并改善游离脂肪酸(FFA)诱导的内质网应激(ERs)。FFA改变的巨自噬(以下简称自噬)也与胰腺β细胞的功能障碍或死亡有关。
我们旨在证明利拉鲁肽通过促进自噬来提高INS-1细胞的存活率。
通过CCK8法评估细胞存活率。Annexin V-FITC/PI染色后,通过流式细胞术测定凋亡细胞的百分比。通过蛋白质免疫印迹法检测LC3的表达。采用单丹磺酰尸胺(MDC)染色和透射电子显微镜(TEM)测量自噬。
利拉鲁肽处理后,INS-1细胞中由棕榈酸(PA)诱导的凋亡得到显著缓解。同时,PA和利拉鲁肽处理增强了自噬。
利拉鲁肽似乎通过促进自噬保护INS-1细胞免受FFA诱导的凋亡。
这些发现为胰高血糖素样肽-1(GLP-1)类似物在预防或治疗T2D方面提供了新的作用。