胡椒碱与小檗碱改善脂肪细胞胰岛素抵抗的比较研究

Comparison of the effects of piperine and berberine on insulin resistance in fat cells

目的:胡椒碱和小檗碱分别是温里药荜茇和清热药黄连的主要成分,二者均可以改善胰岛素抵抗。本研究通过建立3T3-L1脂肪细胞胰岛素抵抗模型[1,2],观察胡椒碱和小檗碱对该细胞模型的糖代谢紊乱的干预作用,意在探讨药效相似、药性相反的胡椒碱是否同小檗碱一样可以通过调节腺苷酸活化蛋白激酶AMPK而改善胰岛素抵抗。方法:诱导3T3-L1脂肪细胞分化为成熟的脂肪细胞后,采用1μM地塞米松作用48h建立脂肪细胞胰岛素抵抗模型,以AMPK激活剂AICAR和罗格列酮为阳性药,观察不同浓度的胡椒碱和小檗碱作用该模型48h后对糖代谢紊乱的调节作用,继而采用Western blot检测药物作用不同时间后细胞中AMPKα的水平变化。结果:胡椒碱、小檗碱同阳性药AICAR、罗格列酮一样在作用该脂肪细胞胰岛素抵抗模型48h后均可改善糖代谢紊乱。Western blot检测结果:与模型组比较,40u M胡椒碱、5u M小檗碱同阳性AICAR一样在作用脂肪细胞胰岛素抵抗模型6h,12h和24h后,P-AMPKα的蛋白表达明显提高。结论:胡椒碱同小檗碱一样能够改善糖代谢紊乱,其机理有可能是通过调节AMPK信号通路中的AMPKα的活性而改善胰岛素抵抗的。

Objective： PIP and BBR, which are main component of piper longu L. and Coptis chinensis Franch. respectively, can reverse insulin resistance. To investigate the effects of PIP and BBR on the glucose metabolism disorder and underlying mechanism that may regulated through AMPK. Methods： Inducing IR cellular model of 3T3-L1 adipocyte by using 1 μM DEX after differentiate into mature adipocytes of pre-adipocyte. Normal cell and IR model of 3T3-L1 were treated with PIP and BBR at different dose, AMPK and ROG were used as positive control. The glucose intake of cells were determined after 48h treatment of drugs, AMPKα protein were determined by western blotting. Re- suits： Glucose consumption and uptake tests showed that in the presence of PIP or BBR, compared with IR group, glucose consumption and uptake rate displayed a remarkable increase in drug group. Western blot assay showed that 40μM PIP and 5μM BBR markedly up-regulated the level of P-AMPKαprotein expression in IR-adipocytes. Conclusion： PIP and BBR might improve IR by targeting AMPK, increasing the level of AMPKα phosphorylation. This study, to a certain extent, reflects the role of PIP in improving IR and the internal mechanism.