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过氧化物酶体增殖物激活受体γ辅助激活因子-1α对不同浓度棕榈酸诱导下INS-1细胞生长及功能改变的影响

来自:中国糖尿病杂志  编辑:刘林 张俊清 冯楠 李薇 郭晓蕙|点击数:|2015-01-28

  【摘要】 目的 观察不同浓度棕榈酸培养INS-1细胞时过氧化物酶体增殖物激活受体γ辅助激活因子-1α(PGC-1α)的表达变化及其与细胞增殖、凋亡和胰岛素分泌能力的关系。 方法 INS-1细胞在50、100、400 μmol/L棕榈酸培养4、8、12、24、48 h检测PGC-1α mRNA及蛋白表达、细胞增殖活力、Bcl-2蛋白、基础及葡萄糖刺激的胰岛素分泌。 结果 50 μmol/L棕榈酸培养时,INS-1细胞PGC-1α mRNA 48 h有增多趋势,但差异无统计学意义;8、12 h 细胞增殖活力减低,24、48 h与对照组比较差异无统计学意义;Bcl-2蛋白表达无变化;48 h基础及葡萄糖刺激胰岛素分泌量增加;100 μmol/L棕榈酸培养时,INS-1细胞PGC-1α mRNA 24 h表达增加,48 h蛋白表达增加;8、12、24 h细胞增殖活力减低,48 h与对照组比较差异无统计学意义;Bcl-2蛋白表达无变化;基础及葡萄糖刺激胰岛素分泌量增加。400 μmol/L棕榈酸培养时,INS-1细胞PGC-1α mRNA 12 h表达增加,24 h后PGC-1α蛋白表达进行性增加;8 h起细胞增殖活力降低;24 h起Bcl-2蛋白表达减少;48 h基础胰岛素分泌及葡萄糖刺激的胰岛素分泌降低。 结论 轻、中度高脂培养条件下INS-1细胞PGC-1α表达轻度增加,与细胞增殖活力改变和胰岛素分泌能力增加相关。重度高脂培养条件下INS-1细胞PGC-1α表达增加,与细胞增殖活力减低、抗凋亡减少和胰岛素分泌能力受损相关,提示PGC-1α可能参与棕榈酸对INS-1细胞增殖、凋亡及功能改变的影响。

  【关键词】过氧化物酶体增殖物激活受体γ辅助激活因子-1α;INS-1细胞;胰岛素分泌;细胞增殖;凋亡

  【Abstract】 Objective To explore the expression of peroxisome proliferator activated receptor γ coactivator-1α (PCG-1α) in INS-1 cells treated with different concentration of palmitic acid and its relationship with cell proliferation, apoptosis and function. Methods INS-1 cells were cultured in RPMI 1640 contained 50, 100 and 400 μmol/L palmitic acid for 4, 8, 12, 24 and 48 h, expression of PGC-1α mRNA and protein, cell proliferation vitaliy, Bcl-2 protein, total supernant insulin concentration, basal and glucose-stimulated insulin concentration were examined. Results In 50 μmol/L palmitic acid group, PGC-1α mRNA showed a trend of increase until 48 h but with no statistical significance; the cell proliferation vitaliy decreased in 8 and 12 h, but had no difference in 24 and 48 h; the expression of Bcl-2 protein had no difference; the basal and glucose-stimulated insulin secretion increased. In 100 μmol/L palmitic acid group, PGC-1α mRNA increased from 24 h and PGC-1α protein increased until 48 h; the cell proliferation vitaliy decreased in 8, 12 and 24 h, but had no difference in 48 h; the expression of Bcl-2 protein had no difference; the basal and glucose-stimulated insulin secretion increased. In 400 μmol/L palmitic acid group, expression of PGC-1α mRNA significantly increased from 12 h and PGC-1α protein increased until 24 h; the MTT decreased from 8 h; the expression of Bcl-2 protein decreased from 24 h; both basal and glucose-stimulated insulin secretion decreased. Conclusion The expression of PGC-1α in 50 and 100 μmol/L palmitic acid had a mild increase, it had a close relationship with the changes of proliferaton vitality and the increased function of insulin secretion. While incubating with 400 μmol/L palmitic acid, the expression of PGC-1α increased significantly, and related to destroyed cell proliferation vitality and insulin secretion function. Our study indicated that PGC-1α played an important role in the changes of cell proliferation, apoptosis and function induced by palmitic acid.

  【Key words】Peroxisome proliferator activated receptor γ coactivator-1α (PCG-1α);INS-1 cell;Insulin secretion;Cell proliferation;Apoptosis

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