摘要
目的研究表没食子儿茶素没食子酸酯(EGCG)对自发性2型糖尿病GK大鼠的胰岛素抵抗的影响及作用机制。方法 自发性2型糖尿病GK大鼠40只,同系健康对照Wistar大鼠10只,大鼠随机分为:正常对照组、2型糖尿病对照组、2型糖尿病低剂量EGCG(50 mg/kg)治疗组、中剂量(100 mg/kg)组、高剂量EGCG(300 mg/kg)组。干预6周后,分别检测葡萄糖耐量试验、胰岛素耐受试验、肝脏GcK、G6P以及PEPCKmRNA表达情况,以及骨骼肌细胞膜GLUT4含量的变化。结果各剂量治疗组的糖耐量均得到明显改善(P<0.05),胰岛素耐量在240 min时较模型对照组有明显差异(P<0.05)。与模型组比较,低剂量和中剂量治疗组均能提高肝脏葡萄糖激酶(GcK)mRNA的表达(P<0.05),同时抑制葡萄糖-6-磷酸酶(G6P)和磷酸烯醇式丙酮酸激酶(PEPCK)mRNA的表达(P<0.05);高剂量治疗组肝脏三类酶mRNA的表达与模型对照组相比无明显差异。各剂量治疗组GK大鼠的骨骼肌细胞膜GLUT4的含量较模型对照组均具有明显上调(P<0.05)。结论中低剂量EGCG可以改善GK大鼠胰岛素抵抗,其作用机制可能与抑制肝脏糖异生作用以及骨骼肌GLUT4的转位水平有关,并且EGCG具有代偿胰岛素的作用。
Objective To investigate the effect of epigallocatechin-3-gallate(EGCG) on insulin-resistance of Goto-Kakizaki rats and the related mechanisms.Methods Goto-Kakizaki diabetic rats(GK,n=40) were observed and Wistar rats(n=10) as control.The rats were randomly divided into five groups: normal control group,type 2 diabetic model group,diabetic model plus EGCG of 50 mg/kg,100 mg/kg and 300 mg/kg therapy groups,respectively.oral glucose tolerance test(OGTT),insulin tolerance test(ITT),the mRNA expression level of GcK,G6P,PEPCK and the in skeletal muscle plasma membrane GLUT4 content were detected at 6 weeks after treatment.Results The OGTT was improved in all three treatment groups(P0.05).There was a significant statistical difference on ITT between diabetic control group and low-to moderate-dose groups at 240 min(P0.05).In comparison with the diabetic control group,the mRNA expression of hepatic GcK gene was significantly increased(P0.05),and the level of mRNA of G6P and PEPCK genes in the liver was significantly decreased in the low-to moderate-dose treatment groups(P0.05),but there was no significant difference in the expression of three kinds of mRNA in the liver between the high-dose treatment group and diabetic control group.the skeletal muscle membrane GLUT4 content in the three treatment groups was significantly higher than that in the diabetic control group(P0.05).Conclusions Low-to moderate-dose EGCG can improve insulin-resistance in type II diabetic rats,and its mechanisms might be closely related to the restriction of liver gluconeogenesis and the elevation of GLUT4 level in the skeletal muscle tissues of rats.EGCG can exert certain campensatory effect of the insulin function.
出处
《中国实验动物学报》
CAS
CSCD
2011年第6期489-494,共6页
Acta Laboratorium Animalis Scientia Sinica