·糖尿病基础研究·

　　【摘要】 目的 研究Exendin-4对棕榈酸(PA)诱导的小鼠胰岛βTC6细胞c-jun氨基末端激酶(JNK)信号转导通路活化及凋亡的影响。 方法 不同浓度PA(0.125, 0.25, 0.5mmol/L)干预βTC6细胞12h, 24h和48h，cck-8法检测增殖活性;将βTC6细胞分为对照组，PA组， PA+SP600125组和PA+Exendin-4组，观察细胞形态学变化;TUNEL法测凋亡;Western blot法测p-JNK, JNK, p-c-jun, c-jun蛋白表达。 结果 (1)随PA浓度升高及干预时间延长，细胞增殖活性逐渐降低。(2)0.5mmol/L PA干预24h后，βTC6细胞凋亡增加(29.3%±2.5%)，JNK, c-jun磷酸化增多。加用SP600125或Exendin-4后，凋亡减少(分别为22.5%±3.2%和18.3%±2.9%)，PA+Exendin-4组p-JNK与p-c-jun表达有所下降。 结论 PA所致的β细胞内JNK及其底物蛋白c-jun磷酸化活化可能是β细胞脂性凋亡的重要环节。Exendin-4可通过抑制β细胞内JNK活化拮抗脂性凋亡。

　　【关键词】 棕榈酸;βTC6细胞;细胞凋亡;c-jun氨基末端激酶信号转导通路

Exendin-4 protects βTC6 cells from lipoapoptosis through inhibiting the activation of JNK signaling pathway XIANG Jing-nan, CHEN Dan-ling, YANG Li-yong. The First Clinical Medical College of Fujian Medical University, Fuzhou 350004, China;

Corresponding author: YANG Li-yong, Email: yly-lm@sina.com

　　【Abstract】Objective To investigate the effect of Exendin-4 on palmitic acid (PA) -induced activation of c-jun NH2-terminal kinase (JNK) signaling pathway and apoptosis in βTC6 cells. Methods βTC6 cells were stimulated with different concentrations (0.125, 0.25, and 0.5mmol/L) of PA for different times (12h, 24h, and 48h), and the cellular proliferation activity was detected by cck-8. βTC6 cells were further treated with PA, or the combination of PA and SP600125, or the combination of PA and Exendin-4. The morphological changes of βTC6 cells were observed by optical microscope, the apoptosis was detected by TUNEL, and the expression of p-JNK, JNK, p-c-jun, and c-jun was examined by Western blot. Results (1) The cellular proliferation activity was decreased when βTC6 cells were stimulated with higher concentration of PA for increasing lengths of time. (2) 24h exposure to PA 0.5mmol/L significantly increased the percentage of apoptotic cells (29.3%±2.5%) as well as the phosphorylation level of JNK and c-jun. The apoptosis of βTC6 cells was reduced after the addition of SP600125 or Exendin-4 (22.5%±3.2% and 18.3%±2.9% respectively). The expression of p-JNK and p-c-jun was partly decreased in the presence of Exendin-4 after 24h exposure to PA 0.5mmol/L. Conclusion The activation of JNK and its substrate protein c-jun may play an important role in PA-mediated β-cell apoptosis. Exendin-4 may protect β cells from lipoapoptosis through inhibiting the activation of JNK signaling pathway.

　　【Key words】Palmitic acid (PA); βTC6 cells; Apoptosis; c-jun NH2-terminal kinase (JNK) signaling pathway