代平颗粒对2型糖尿病大鼠血糖、血脂水平及骨骼肌Glut4 mRNA,IRS-1 mRNA表达的影响

目的:观察中药代平颗粒对2型糖尿病大鼠骨骼肌葡萄糖转运蛋白4( Glut4)、胰岛素受体底物1(IRS-1)基因表达的影响,初步探讨其降低血糖的分子机制.方法:雄性SD大鼠分为正常对照组(8只,普通饲料),其余大鼠采用高脂饲料喂养联合链脲佐菌素(STZ)尾静脉注射的方法造成2型糖尿病成膜大鼠(32只),分为模型组(M)、二甲双胍组(Met)、代平颗粒低剂量组(DL),代平颗粒高剂量组(DH),每组8只.经药物干预4周后检测各组大鼠空腹血糖( FBG)、血脂、空腹胰岛素(FINS)并计算胰岛素敏感指数(ISI),采用实时荧光定量PCR技术检测大鼠骨骼肌Glut4 mRNA,IRS-1 mRNA表达水平.结果:给药后4周,与M组FBG:( 20.55±5.50) mmol·L -1,ISI:(-6.05±0.29)比较,Met组FBG(14.75±3.90)mmol·L-1和DH组FBG(11.21±2.95) mmol·L-1均显著下降(P＜0.01),Met组ISI(-5.37±0.38)和DH组ISI(-5.38±0.37)均显著升高(P＜0.01)；M组Glut4 mRNA(0.63±0.13)和IRS-1 mRNA (0.68±0.17)表达量分别为N组的63.3％,67.8％(P＜0.01)；与M组比较,Met组Glut4 mRNA(0.95±0.19)表达量升高了31％ (P ＜0.01),IRS-1 mRNA (0.88±0.24)表达量无显著升高,DH组Glut4 mRNA(1.19±0.15)和IRS-1 mRNA(1.24±0.22)表达量,分别升高了88.9％,82.4％(P＜0.01).结论:代平颗粒具有降低2型糖尿病大鼠FBG效果,其作用机制之一与增加组织胰岛素敏感性,上调2型糖尿病大鼠骨骼肌中Glut4 mRNA和IRS-1 mRNA的表达,促进骨骼肌对葡萄糖的摄取和利用有关.

Effect of Daiping Granules on Blood Glucose, Blood Lipid and Gene Expression of Glut4 and IRS-1 in Skeletal Muscle of Rats with Type 2 Diabetes

Objective: To investigate the effect of Daiping granules on the gene expression of Glut4 and IRS-1 in skeletal muscle of rats with type 2 diabetes and explore its possible molecular mechanism in decreasing the blood sugar. Method: The rat type 2 diabetes model was established by feeding with high-fat diets and injecting streptozocin (STZ) into caudal vein. The model rats were randomly divided into model group (M), Metformine group (Met), Daiping granules low dose group (DL), Daiping Granuleshigh dose group (DH),at the same time normal control group (N) was established. After four weeks of treatment, blood was collected for measurement of fasting blood glucose(FBG),serum lipid and fasting insulin(FINS), and insulin sensitivity index(ISI) was calculated.Real-time quantitative PCR technology was employed to measure Glut4 mRNA and IRS-1 mRNA expression of in the skeletal muscle. Result: After 4 weeks of dosing,compared with M group·L^-1,ISI:(-6.05±0.29)], FBG·L^-1,DH:(11.21±2.95)mmol·L^-1] was decreased significantly(P<0.01) and ISI was increased (P<0.01) in Met group and DH group. Contents of Glut4 mRNA and IRS-1 mRNA in M group were respectively 63.3%,67.8%(P<0.01);compared with M group, contents of Glut4 mRNA were increased 31%(P<0.01)and IRS-1 mRNA were not significantly increased(P>0.05)in Met group;while contents of Glut4 mRNA and IRS-1 mRNA in DH group were,respectively,increased 88.9% (P<0.01)and 82.4%( P<0.01). Conclusion: Daiping granules has a good effect on decreasing FBG in rats with type 2 diabetes, and its mechanism is probably related to increasing insulin sensitivity of the target tissues, enhancing the expressional level of Glut4 mRNA and IRS-1 mRNA in skeletal muscle and improving the taking in and metabolism of blood glucose.