摘要
目的探讨小檗碱改善糖尿病鼠糖代谢及胰岛素抵抗作用及对骨骼肌线粒体功能的影响和机制。方法采用db/db小鼠为研究对象,以野生型小鼠为对照组。给予小檗碱(5 mg·kg-1·d-1)腹腔注射3周,观察食量、体重和空腹血糖水平;第3周末处死,留取血标本分离血清,检测胰岛素水平并计算胰岛敏感指数,留取附睾脂肪垫并称重;提取腓肠肌线粒体,检测细胞色素C氧化酶活性和ATP定量,Western blot检测腓肠肌AMPK/PGC-1α表达。结果小檗碱给药3周后,db/db小鼠的体重和脂肪垫重量均显著降低,血糖水平下降,胰岛素敏感指数改善;但给药前后的胰岛素释放水平无明显改变。小檗碱可一定程度地升高骨骼肌线粒体COX活性水平,明显提高ATP含量,并使AMPK磷酸化水平显著激活,PGC-1α转录活性增强。结论小檗碱具有明显的降糖、降脂、改善胰岛素抵抗作用,其降糖作用与刺激胰岛素释放水平无关,而与激活AMPK/PGC-1α信号途径,提高线粒体能量代谢有关。
Objective To investigate Berberine improve metabolism and insulin resistant in db/db mice and effects on skeletal muscle mitochondrial function, and relative mechanisms. Methods We selected db/db mouse as model of diabetes/insulin-resistance, the wild type mouse as control group. The db/db mice were administrated with berberine(5 mg·kg-1·d-1) by intraperitoneal injection till three weeks. The food intake, body weight and fasting blood glucose levels were observed every week. At 3rd weekend, all the mice were sacrificed, blood serum sample was collected for measurement the fasting insulin level by ELISA, then calculation of insulin sensitivity index (ISI). The epididymal fat pads were separation and weighed. The gastrocnemius was extracted mitochondria and measured the cytochrome C oxidase activity and ATP content. The gastrocnemius AMPK/PGC-1-αexpression was detected by Western blot. Results The body weight and fat weight of db/db mice decreased dramatically after treated with berberine. Berberine showed lowering fast blood glucose and improving the ISI. No significant change in serum insulin release before or after Berberine treated. Berberine increased the COX activity and ATP content in skeletal muscle mitochondria. We also observed the AMPK phosphorylation was significantly activated and the nucleus transcriptional PGC-1αincreased. Conclusion Berberine obviously improved insulin-resistance by lower blood glucose, body weight and fat weight. These effects showed no relationship to insulin release, but related to increase mitochondria energy metabolism by active AMPK/PGC-1αsignaling.
出处
《中华临床医师杂志(电子版)》
CAS
2014年第5期69-73,共5页
Chinese Journal of Clinicians(Electronic Edition)
基金
上海浦江人才计划基金(10PJD016)
上海市卫生局中西医结合重点病种项目(ZXBZ2012-17)
关键词
小檗碱
糖尿病
线粒体
胰岛素抵抗
AMPK
AMPK
Berberine
Diabetes mellitus
Mitochondria
Insulin resistance
AMPK