表没食子儿茶素没食子酸酯对2型糖尿病大鼠GLUT2/G6PD/GS表达和血糖调节的研究

Effects of EGCG on GLUT2/G6PD/GS expression and blood glucose level in type 2 diabetic rats

目的:探讨表没食子儿茶素没食子酸酯(EGCG)是否通过葡萄糖转运蛋白2(GLUT2)-葡萄糖6-磷酸脱氢酶(G6PD)-糖原合酶(GS)途径改善2型糖尿病大鼠血糖。方法:采用高脂饲养+小剂量链脲佐菌素(STZ)制备2型糖尿病SD大鼠模型,成模后采用数字随机法分为糖尿病模型(M)组、二甲双胍(Met)组、EGCG低剂量(EL)组和EGCG高剂量(EH)组,另设正常对照(Con)组,每组10只,治疗组给予相应药物干预8周,其余2组均灌服生理盐水(0.1 mL/kg),8周后处死大鼠,收集血液和肝脏组织。检测各组大鼠空腹血糖(FBG)、空腹血清胰岛素(FINS)和糖化血红蛋白;采用PAS染色检查肝糖原含量;real-time PCR检测G6PD mRNA的表达;Western blot和免疫组化检测GS和GLUT2蛋白水平。结果:成功建立2型糖尿病大鼠模型。与Con组比较,M组大鼠FBG、FINS和糖化血红蛋白明显升高(P<0.05),胰岛素敏感指数(ISI)、肝糖原含量、G6PD mRNA表达水平、GS蛋白表达水平和GLUT2蛋白表达水平均显著降低(P<0.05)。与M组比较,给药组大鼠FBG和糖化血红蛋白水平显著降低(P<0.05),ISI、肝糖原含量、G6PD mRNA表达水平、GS蛋白表达水平和GLUT2蛋白表达水平均显著升高(P<0.05)。结论:EGCG对2型糖尿病大鼠有显著的降血糖作用,其机制可能与GLUT2-G6P-GS信号通路有关。

AIM:To investigate whether epigallocatechin gallate(EGCG)improves blood glucose in type 2 diabetic rats through glucose transporter 2(GLUT2)-glucose-6-phosphate dehydrogenase(G6PD)-glycogen synthase(GS)pathway.METHODS:Type 2 diabetes mellitus(T2DM)model was established in male Sprague-Dawley(SD)rats by feeding with high-fat diet and injection of streptozotocin(STZ).The rats were divided into 5 groups(n=10):control(Con)group,T2DM model(M)group,metformin(Met;200 mg/kg,ig)group,T2DM+low-dose(50 mg/kg,ig)EGCG(EL)group,and T2DM+high-dose(100 mg/kg,ig)EGCG(EH)group.Diabetic rats were given drugs for 8 weeks.Af⁃ter 8 weeks of administration,the rats were killed,and the blood and liver tissues were collected.The levels of fasting blood glucose(FBG),fasting serum insulin(FINS)and serum glycosylated hemoglobin were measured by biochemical tests.Liver glycogen were test by periodic acid-Schiff(PAS)staining.The mRNA expression of G6PD in the liver was de⁃tected by real-time PCR.The protein levels of GS and GLUT2 were determined by Western blot and immunohistochemis⁃try.RESULTS:T2DM rat model was established successfully.Compared with Con group,the levels of FBG,FINS and serum glycosylated hemoglobin in M group were increased significantly(P<0.05),while the insulin sensitivity index (ISI),the liver glycogen,the G6PD mRNA expression,and the protein levels of GS and GLUT2 were decreased signifi⁃cantly(P<0. 05). Compared with M group,the levels of FBG and serum glycosylated hemoglobin in Met group and EHgroup were decreased significantly(P<0. 05),while the ISI,the liver glycogen,the G6PD mRNA expression,and theprotein levels of GS and GLUT2 were increased significantly(P<0. 05). CONCLUSION:EGCG reduces the blood glu⁃cose level in T2DM rats,which may be related to the regulation of GLUT2-G6PD-GS signaling pathway.