6-姜烯酚改善db/db小鼠胰岛素敏感性研究

Research of 6-shogaol on Improving Insulin Sensitivity in Db/Db Mice

目的:研究6-姜烯酚对db/db小鼠肝脏组织胰岛素敏感性的影响及机制。方法:将24只db/db小鼠(雌雄各半)随机分为模型组、6-姜烯酚低剂量组(10mg·kg^(-1))、6-姜烯酚高剂量组(40mg·kg^(-1)),另取BKS小鼠8只(雌雄各半)作为正常对照组,连续灌胃给药3周。于2周末行葡萄糖耐量OGTT实验,取血测定血浆葡萄糖、胰岛素含量,计算HOMA-IR及HOMA-IS指数;第3周末处死动物取肝脏组织,RT-PCR法及Western blot检测肝脏组织糖异生及胰岛素信号相关基因及蛋白的表达。结果:6-姜烯酚下调db/db小鼠禁食血浆葡萄糖、胰岛素水平,降低胰岛素抵抗指数(HOMA-IR),升高胰岛素敏感性指数(HOMA-IS)。同时,6-姜烯酚逆转了db/db小鼠肝脏糖异生的关键基因(磷酸烯醇式丙酮酸羧激酶PEPCK和葡萄糖6-磷酸酶G6PC)高表达(P<0.05),明显升高了线粒体质量控制蛋白1α(PGC-1α)和葡萄糖转运蛋白2(GLUT2)的表达。结论:6-姜烯酚能改善db/db小鼠胰岛素敏感性,可能与调节糖异生关键酶PEPCK、G6PC和PGC1-α、GLUT2胰岛素信号通路有关。

Objective:To investigate the effect and mechanism of 6-shogaol on hepatic insulin sensitivity in db/db mice.Methods:Twenty-four db/db mice(twelve animals per sex)were randomized into db/db mice group,low-dose 6-shogaol group,and high-dose 6-shogaol group(10 mg·kg^(-1),40 mg·kg^(-1),ig.for 3 weeks),four animals per sex in each group;Eight BKS mice(four animals per sex)were taken as normal control group.Enzymatic method and ELISA were used for the examination of plasma glucose,OGTT,triglycerides,insulin concentrations and HOMA-IR,HOMA-IS index.The RT-PCR and Western Blot were used for the determination of the gluconeogenesis genes and factors related to insulin signaling pathways in liver tissue.Results:The treatment of 6-shogaol(40 mg·kg^(-1))could decrease plasma glucose,insulin concentrations,triglycerides,the insulin resistance index(HOMA-IR)as well as increase the insulin sensitivity index(HOMA-IS)in db/db mice.Meanwhile,6-shogaol(40 mg·kg^(-1))suppressed the high expression of the genes of hepatic gluconeogenesis(phosphoenolpyruvate carboxykinase PEPCK and glucose 6-phosphatase G6PC)in db/db mice(P<0.05).The expression of mitochondrial quality control protein(PGC)1-αand glucose transporter(GLUT)2 were increased by the treatment of 6-shogaol(40 mg·kg^(-1)).Conclusion:6-shogaol may improve the insulin sensitivity in db/db mice,which is associated withdown-regulating the expression of PEPCK,G6PC and up-regulating the expression of PGC1-α,GLUT2 in liver.