小檗碱对胰岛素抵抗大鼠肝脏葡萄糖激酶及其调节蛋白的影响

Effect of berberine on hepatic giucokinase and its regulatory protein in insulin-resistant rats

目的:研究小檗碱对胰岛素抵抗大鼠肝脏葡萄糖激酶(GK)活性及肝脏GK与葡萄糖激酶调节蛋白(GKRP)表达的影响．方法:选用♂Wistar大鼠,以高脂高热量饲料喂养8 wk,复制胰岛素抵抗大鼠模型,成模后随机分成模型组、小檗碱组、二甲双胍组,各药干预4 wk后,比较各组大鼠胰岛素敏感性、肝糖原、肝脏GK活性、肝脏GK与GKRP蛋白(Western blot法)表达的差异．结果:比模型组比较,小檗碱组胰岛素敏感性提高(-4．93±0．30 vs-5．35±0．40,P<0．05),肝糖原含量明显升高(136．58±52．57μg／g vs 65．88±27．80μg／g,P<0．05),肝脏GK活性升高(226．55±10．62μkat／g vs 92．69±6．43μkat／g, P<0．05),肝脏GK蛋白表达增强(1．71±0．49 vs 1．24±0．22,P<0．05),而GKRP表达减弱(1．19±0．20 vs．94±0．56,P<0．01):与二甲双胍组比较,小檗碱组肝糖原含量高(136．584±52．574μg/g vs 89．427±31．971μg/g,P<0．05),余指标无显著性差异(P>0．05)．结论:小檗碱改善胰岛素抵抗的作用机制可能与提高肝脏GK活性有关．

AIM： To investigate the effects of berberine on hepatic glucokinase （GK） activity, protein expression and GK＇s regulatory protein （GKRP） in insulin-resistant rats. METHODS： Male Wistar rats were fed with high-fat diet for 8 weeks to induce the model of insulin resistance. Then the insulin-resistant rats were randomly divided into 3 groups： model, berberine, and metformin groups which were treated with the corresponding preparations. Meanwhile, a normal control group was designed. The differences in insulin sensitivity, hepatic glycogen, hepatic GK activity, and protein expression （using Western blot） of hepatic GK and GKRP were compared among the groups.RESULTS： As compared with those in model group, the insulin sensitivity （-4.93 ± 0.30 vs -5.35 ± 0.40, P 〈 0.05）, hepatic glycogen level （136.58 ± 52.57 μg/g vs 65.88 ± 27.80 μg/g, P 〈 0.05）, GK activity （226.55 ± 10.62 μkat/g vs 92.69 ± 6.43 μkat/g, P 〈 0.05）, and hepatic GK protein expression （1.71 ±0.49 vs 1.24±0.22, P 〈 0.05） were significantly elevated in berberine group, while the expression of GKRP protein weaker （1.19 ± 0.20 vs 1.94 ± 0.56, P 〈 0.01）. Meanwhile, the hepatic glycogen level in berberine group was markedly higher than that in mefformin group （136.584 ± 52.574 μg/g vs 89.427 ± 31.971 μg/g, P 〈 0.05）, but the other indexes were not significantly different between them （all P 〉 0.05）. CONCLUSION： Berberine may decrease insulin resistance by increasing of the hepatic GK activity.