吡格列酮对游离脂肪酸介导的β细胞胰岛素分泌的双向调节作用研究

Bidirectional regulative effects of pioglitazone on free fatty acids-induced impairment of insulin secretion

目的探讨吡格列酮对游离脂肪酸(FFA)作用不同时间介导的β细胞胰岛素分泌异常的干预效果。方法βTC3细胞分为对照组(Con组)、FFA干预组(FFA组)和FFA加吡格列酮共同干预组(FFA+Pio组),分别干预1、72h,放射免疫法检测不同糖浓度刺激的胰岛素分泌,巢式RT-PCR检测FFA受体1(FFA1R)mRNA的表达。结果干预1h,与Con组比较,FFA组低、中、高糖刺激的胰岛素分泌升高(分别为23.8±1.6 vs 20.0±2.0,28.7±1.4 vs 24.5±1.5,51.0±3.0 vs 42.6±3.4,P<0.05),FFA+Pio组与Con组相比无统计学差异,三组FFA1R表达均无差异。干预72h,FFA组低、中、高糖刺激的胰岛素分泌(分别为20.0±2.0,24.5±1.5,42.6±3.4)和FFA1R表达均较Con组低(P<0.05),FFA+Pio组的胰岛素分泌和FFA1R表达介于FFA组与Con组之间。结论吡格列酮对FFA作用不同时间介导的胰岛素分泌损害具有双向调节作用,其长时间作用可能与调节FFA1R表达有关。

Objective To investigate effects of pioglitazone（Pio） on the acute and chronic impairment of insulin secretion （IS） by free fatty acids. Methods βTC3 cells were divided into control group, FFAs group and FFAs ＋ Pio group, and cultured in vitro for 1h, 72h. Insulin releasing test was performed. Insulin level was examined by radioimmunoassay, the mRNA of free fatty acid receptor 1 （FFA1R） was detected by reverse transcription polyrnerase chain reaction （RT-PCR）. Results In 1 hour intervention test, FFA group versus control showed the increases of insulin secretion [mU/（L · mg pro）] at 5. 6mmol/L glucose [（23. 8± 1.6） vs （20.0±2.0）],at 11, 2mmol/L glucose [（28. 7±1. 4） vs （24. 5±1. 5）], and at 25mmol/L glucose [（51.0±3. 0） vs （42. 6 ±3. 4）] （all P〈0. 05）. In 72 hours intervention test,the similar responses occurred as in 1 hour intervention. FFA plus pioglitazone versus FFA group in both 1 and 72h showed no effect on insulin secretion （IS） at 5. 6 and 11. 2mmol/L glucose and showed an inhibitive effect on IS at 25mmol/L glucose. The mRNA expressions of FFA1R were not varied in each intervention group in 1 h test; and in 72 h the mRNA content of FFA1R was decreased in FFAs group（P〈0. 05） ,IS and FFAIR expression in Pio ＋ FFAs group was between the levels in FFAs group and control group. Conclusions Pioglitozone appears to have bidirectional regulative effect on the free fatty acidsinduced impairment of insulin secretion during different action times.