胰升血糖素样肽1对胰岛β细胞脂性凋亡的拮抗作用及机制

The protective effects of GLP-1 on fatty acid-induced pancreatic β-cell apoptosis and the potential mechanisms

目的观察棕榈酸盐对胰岛β细胞凋亡及胰腺衍生因子(PANDER)的影响,并观察胰升血糖素样肽1(GLP-1)对其的干预。方法培养β3-TC3细胞分别以PA、PA+GLP-1以及空白处理24 h,以MTT法、Annexin-V/PI荧光染色流式细胞术、Tune1荧光染色法检测细胞凋亡,以RT-PCR法测定PANDER mRNA的表达。结果 PA浓度达0.25 mmol/L时细胞存活率开始显著下降,并随浓度上升逐渐下降(P<0.05)。GLP-1能显著拮抗PA致胰岛3细胞凋亡;PA能明显增加PANDER mRNA的水平,而GLP-1能显著抑制PA对PANDER的作用。结论 PA在诱导胰岛β细胞凋亡的同时刺激PANDER表达,GLP-1拮抗PA致胰岛β细胞凋亡及PANDER的表达;PANDER可能是GLP-1拮抗胰岛β细胞脂性凋亡的靶点之一。

Objective To observe the effects of palmitate （PA） on the pancreatic β-cell apoptosis and PANDER mRNA expression, and the effects of GLP-1 on fatty acid-induced pancreatic β-eell apoptosis and PANDER expression. Methods β-TC3 cells were cultured with vehicle （control）, 0. 5 mmol/L PA, 0. 5 mmol/L PA ＋ 10 nmol/L GLP-1, respectively for 24 hours. Cell apoptosis were evaluated with MTT, Annexin-V-FITC/PI FACS and Tunel assay. PANDER mRNA expression were measured by RT- PCR. Results MTT analysis showed that PA inhibited β-TC3 cell viability in a dose dependent manner with the significantly viability decrease beginning at 0.25 mmol/L PA. GLP-1 counteracted the apoptotic effects of PA on β-TC3 cell. PANDER mRNA increased significantly in PA treated cells （vs eontrol,P〈 0. 05）, while GLP-1 inhibited PA induced PANDER mRNA over expression. Conclusion FFA induces pancreatic β-cells apoptosis and PANDER over expression, GLP-1 counteracts the effects of FFA on pancreatic β-cell and PANDER expression. PANDER may be an important mediator in the signaling pathway of lipoapoptosis of pancreatic beta-cell.