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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

来自:中国糖尿病资讯网  编辑:lj|点击数:|2011-10-20

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

·糖尿病基础研究·

陈松锦 曹筱佩 陈说 肖海鹏 李延兵

基金项目:国家自然科学基金资助项目(30570887)

作者单位:510080广州,中山大学附属第一医院内分泌科

通讯作者:曹筱佩,E-mail: caoxp100@hotmail.com

【摘要】 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β-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、Tunel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β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。

doi:10.3969/j.issn.1006-6187.2011.04.017

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

CHEN Song-jin, CAO Xiao-pei, CHEN Shuo, et al. Department of Endocrinology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China

Corresponding author: CAO Xiao-pei, E-mail: caoxp100@hotmail.com

【Abstract】 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-cell 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 control,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.

【Key words】GLP-1; PANDER; FFA; Islet cells; Apoptosis

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