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过氧化物酶体增生因子激活受体α和γ配体对游离脂肪酸介导的β细胞损害的干预作用 被引量:1

The effect of peroxisome proliferator-activated receptor α and γ ligands on free fatty acid-induced INS-1 cell impairment
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摘要 目的 研究过氧化物酶体增生因子激活受体α和γ (PPARα和PPARγ)配体对游离脂肪酸 (FFA)介导的胰岛 β细胞损害的干预作用。方法 应用PPARα配体氯贝丁酯及PPARγ配体曲格列酮 (troglitazone,TGZ)和噻唑烷二酮 (thiazolidinedione,TZD)处理大鼠胰岛素瘤细胞系 β细胞(INS 1细胞 ) ,采用细胞活力和DNA片段梯度分析评价PPARα和PPARγ配体对FFA诱导的INS 1细胞损害的影响。结果 INS 1细胞与 0 .2 5~ 1mmol/L的FFA孵育 2 4h后细胞活力下降 ,1mmol/L的FFA可诱导INS 1细胞发生凋亡。比较是否使用氯贝丁酯 (10 0 μmol/L)、TGZ (10 μmol/L)和TZD (10 0 μmol/L)处理 β细胞的结果 ,发现这些配体可保护INS 1细胞免于FFA的细胞毒性 (包括脂性凋亡 )作用。结论 FFA可介导 β细胞发生明显的脂毒性和脂性凋亡 ,应用PPARα和PPARγ配体可能具有保护 β细胞免于FFA的细胞毒性的作用。 Objective To investigate the effect of peroxisome proliferator -activated receptor α and γ (PPARα and PPARγ) ligands on free fatty acid (FFA)-induced pancreatic β-cell impairment. Methods Insulinoma cell line β-cell (INS-1 cells) were treated with PPARα ligand (clofibrate) and PPARγ ligands (troglitazone and thiazolidinedione). C, N diphenyl-N′-[4,5- dimethylthiazol-2-yl]- 2,5-diphenyltetrazolium bromide (MTT) viability assay and DNA fragmentation analysis were used to evaluate the effect of PPARα and PPARγ ligands on FFA-induced INS-1 cell impairment. Results The viability of INS-1 cells decreased after incubation of the cells with FFA (0.25~1 mmol/L) for 24 hours. FFA (1 mmol/L) was also found to induce INS-1 cell apoptosis. Comparison of the cells treated with or without clofibrate (100 μmol/L), troglitazone (10 μmol/L) and thiazolidinedione (100 μmol/L), we found that these PPARα and PPARγ ligands could protect INS-1 cells from the cytotoxicity of FFA, including lipoapoptosis. Conclusion FFA mediates significant lipotoxicity and lipoapoptosis in β-cells and application of PPARα and PPARγ ligands might be of value in protection of β-cells from FFA cytotoxicity.
出处 《中华内科杂志》 CAS CSCD 北大核心 2003年第12期847-850,共4页 Chinese Journal of Internal Medicine
关键词 过氧化物酶体增生因子激活受体α γ配体 游离脂肪酸 介导 Β细胞 干预作用 胰岛素瘤 Fatty acids, nonesterified Insulinoma Ligands Receptors, peroxisome proliferators
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  • 1J. D. McGarry,R. L. Dobbins. Fatty acids, lipotoxicity and insulin secretion[J] 1999,Diabetologia(2):128~138
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同被引文献6

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  • 6Ricote M, Li AC, Willson TM, et al. The peroxisome proliferator-activated receptor γ is a negative regulator of macrophage activation. Nature,1998,391:79-82.

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