中文摘要：

目的 观察游离脂肪酸（FFA）对胰岛β-TC3细胞胰腺衍生因子（PANDER）表达的影响,并探讨胰高血糖素样多肽1（GLP-1）对其的拮抗作用及与蛋白激酶B（Akt）信号通路的关系.方法 培养β-TC3细胞,以不同浓度棕榈酸（PA）处理12 h,0.5 mmol/L的PA处理不同时间后实时荧光定量PCR法检测PANDER mRNA表达;Western印迹检测对照组、PA组、PA＋GLP-1组、GLP-1组处理12 h后PANDER、P-Akt及半胱氨酸天冬氨酸蛋白酶-3酶原蛋白表达;在上述各组加入Akt特异阻断剂（Akti-1/2）后,再检测PANDER蛋白表达,并以Hoechst33258核染色法检测细胞凋亡情况.结果 （1）PA浓度依赖性及时间依赖性增加PANDER mRNA表达（P〈0.05）;（2）与对照组（100%）比较,PA组诱导PANDER蛋白表达高[（148±18）%,P〈0.05）,PA＋GLP-1组PA诱导PANDER表达为[（70±17）%,P〈0.01];（3）Akti-1/2减弱GLP-1抑制PA诱导的PANDER表达及细胞凋亡的效应：PA＋GLP-1＋Akti-1/2组较PA＋GLP-1组PANDER蛋白显著高[（249＋49）%比（110±54）%,P〈0.01],细胞凋亡率显著高[（37.8±1.5）%比（20.1±3.5）%,P〈0.01].结论 PA可诱导PANDER的表达及胰岛B细胞凋亡,GLP-1通过激活Akt通路拮抗PA诱导的PANDER表达及胰岛B细胞凋亡.

英文摘要：

Objective To investigate the effects of free fatty acid（FFA）on the expression of pancreatic derived factor（PANDER）in β-cells and to explore the possible relationship between PANDER and Akt signaling pathway at the anti-apoptotic effects of glucagon-like peptide-l（GLP-1）.Methods β-TC3 cells were cultured in vitro witH palmitic acid（PA）of different concentrations and different time courses.The expression of PANDER mRNA was analyzed by realtime quantitative PCR β-TC3 cells were cultured with vehicle.0.5 mmol/L PA.0.5 mmol/L PA＋10 nmol/L GLP-1 and 10nmol/L GLP-1respectively with or without Akti-1/2, a selective inhibitor of Akt, for 12 hours.The protein levels of PANDER, P-Akt and pro-caspase3 were detected by Western blot And cell apoptosis was analyzed by Hoechst33258 staining.Results （1）PA could dose and time dependently increased the expression of PANDER mRNA in β cells（vs control, P〈0.05）;（2）PA increased the PANDER protein expression [（148±18）%vs control 100%.P〈0.05].However,these effects were attenuated by GLP-1 [（70±17）%vs PA group,P〈0.01];（3）Akt inhibitor-1/2 alleviated the effects of GLP-1 on PA inducing the expression of PANDER.The expression of PANDER increased significantly in PA＋GLP-1＋Akti-1/2 group [（249±49）%vs PA＋GLP-1 group（110±54）%,P〈0.01],and cell apoptosis increased significantly as well[（37.8±1.5）%vs PA＋GLP-1 group（20.1±3.5）%,P〈0.01].Conclusion PA induces the expression of PANDER and the apoptosis of β cell while GLP-1 counteracts the above effects through an activation of Akt signaling pathway.