胰高血糖素样肽-1通过抑制糖原合成酶激酶-3β活性保护内质网应激诱导的β细胞凋亡  

GLP-1 protects β cells from endoplasmic reticulum stress-induced apoptosis via inhibition of GSK-3β

作　　者：王猛[1,2] 张文健[2] 许世清[2] 彭亮[2] 王在[2] 刘虹麟[2] 房青[2] 邓婷婷[2] 娄晋宁[2,1] 

机构地区：[1]中国医学科学院北京协和医学院研究生院,北京100730 [2]中日友好医院临床医学研究所,北京100029

出　　处：《中日友好医院学报》2016年第3期157-160,I0001,共5页Journal of China-Japan Friendship Hospital

基　　金：973计划No.2012CB966402;国家自然科学基金No.81370918;北京市自然科学基金No.7122160

摘　　要：目的:探讨胰高血糖素样肽-1(GLP-1)对内质网应激诱导的胰岛β细胞系INS-1细胞凋亡的影响及其机制。方法:培养INS-1细胞,接种后分组:正常对照组、0.1μM毒胡萝卜素(TG)处理组、0.5μM TG处理组、1μM TG处理组、GLP-1(10n M)处理组、TG+GLP-1处理组、SB415286(10μM)处理组和TG+SB415286处理组。细胞处理后,TUNEL染色法检测细胞凋亡,Western blot检测蛋白表达水平。结果:与正常对照组相比,TG组INS-1细胞凋亡率均显著升高(P<0.05,P<0.01),随着TG浓度的增加Caspase-3活性逐渐升高。与TG处理组相比,TG和GLP-1共同处理组INS-1细胞凋亡率显著下降(P<0.01),且Caspase-3活性下降;TG和GLP-1共同处理组糖原合成酶激酶-3β(GSK-3β)的活性下降。TG和SB415286共同处理组INS-1细胞凋亡率显著下降(P<0.05),且Caspase-3活性下降。结论 :GLP-1可以通过抑制GSK-3β活性减轻内质网应激引起的损伤从而保护β细胞。Objective：To investigate the effect of glucagon-like peptide-1（GLP-1）on apoptosis induced by endoplasmic reticulum stress（ER stress）and its mechanism in pancreatic β cell line INS-1 β-cells.Methods：INS-1 cells were cultured and seeded, and were divided into different groups for treatment： the INS-1 cells were divided into control group,0.1μM Thapsigargin（TG）-treated group,0.5μM TG-treated group, 1μM TGtreated group;GLP-1-treated group,TG and GLP-1 co-treated group;SB415286-treated group,TG and SB415286 co-treated group.After treatment,TUNEL staining was used to detect the apoptosis rate,Western blot was used to detect the levels of protein.Results：（1）Compared with control group,INS-1 cell apoptosis rate in TG-treated group were significantly increased（P〈 0.05,P〈 0.01）with dose-dependent manner.（2）INS-1 cell apoptosis rate in TG and GLP-1 co-treated group was significantly decreased as compared with that in the control group（P〈0.01）,and the Caspase-3 activity was decreased.（3）Compared with TG-treated group,the activity of glycogen synthase kinase-3β（GSK-3β）in TG and GLP-1 co-treated group was decreased.（4）INS-1cell apoptosis rate in TG and SB415286 co-treated group was significantly decreased as compared with that in control group（P〈0.05）,and the Caspase-3 activity was decreased.Conclusion：GLP-1 could protect β cells from endoplasmic reticulum stress-induced apoptosis by inhibiting GSK-3β activity.

关 键 词：胰高血糖素样肽-1 内质网应激 Β细胞 糖原合成酶激酶-3Β 

分 类 号：R587.1[医药卫生—内分泌]