基于PI3K/Akt/AS160/GLUT4通路探讨芪丹颗粒改善2型糖尿病大鼠胰岛素抵抗的作用机制

Exploring the Effects and Mechanisms of Qidan Granules in Improving Insulin Resistance in Type 2 Diabetic Rats Based on the PI3K/Akt/AS160/GLUT4 Signaling Pathway

【目的】探讨芪丹颗粒对2型糖尿病(T2DM)大鼠模型胰岛素抵抗(IR)的治疗作用与机制。【方法】实验分5组:正常组、模型组、芪丹颗粒低剂量组、芪丹颗粒高剂量组及二甲双胍组。除正常组,其他各组采用高糖高脂饲料喂养结合腹腔注射链脲佐菌素(STZ)法建立2型糖尿病大鼠模型。对应给药后,检查各组大鼠体质量,空腹血糖,血脂谱[总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)]及稳态模型评估的胰岛素抵抗指数(HOMAIR),分别采用实时定量聚合酶链反应(qRT-PCR)、Western Blot法对应检测肝脏组织中磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、160 kDa的Akt底物(AS160)和葡萄糖转运体4(GLUT4)的mRNA、蛋白表达变化。【结果】芪丹颗粒干预后可降低2型糖尿病大鼠体质量、空腹血糖值,改善TC、TG、HDL-C、LDL-C水平,降低HOMA-IR值,上调肝脏组织PI3K、Akt、GLUT4的mRNA表达量,上调肝脏组织p-PI3K、Akt、p-Akt、p-AS160、GLUT4的蛋白表达量,差异均有统计学意义(P<0.05),且对指标的改善作用与二甲双胍相当(P>0.05)。【结论】芪丹颗粒可改善2型糖尿病大鼠胰岛素抵抗,其机制与促进PI3K/Akt/AS160/GLUT4信号通路激活有关。

Objective To investigate the therapeutic effect and mechanism of Qidan Granules on insulin resistance(IR)in rat model of type 2 diabetes mellitus(T2DM).Methods The experiment was divided into five groups:the normal group,the model group,the low-dose group of Qidan Granules,the high-dose group of Qidan Granules and the metformin group.Except for the normal group,the other groups used high-sugar and high-fat feeding combined with intraperitoneal injection of streptozotocin(STZ)method to establish a T2DM rat model.After corresponding drug administration,body mass,fasting blood glucose,lipid profile[total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDLC)]and homeostasis model assessment of insulin resistance index(HOMA-IR)were examined in each group,the real-time quantitative polymerase chain reaction(qRT-PCR)and Western Blot methods corresponded to detect the mRNA and protein expression changes of phosphoinositide 3-kinase(PI3K),protein kinase B(Akt),Akt substrate of 160 kDa(AS160)and glucose transporter 4(GLUT4)in liver tissue,respectively.Results The intervention of Qidan Granules could reduce the body mass and fasting blood glucose value,improve the levels of TC,TG,HDL-C and LDL-C,reduce the HOMA-IR value,up-regulate the mRNA expressions of PI3K,Akt and GLUT4 in liver tissue,and up-regulate the protein expressions of p-PI3K,Akt,p-Akt,p-AS160 and GLUT4 in liver tissue in T2DM rats,and the differences were statistically significant(P<0.05),and the improvement effect on indicators is comparable to that of metformin(P>0.05).Conclusion Qidan Granules can improve insulin resistance in T2DM rats,and the mechanism is related to the activation of PI3K/Akt/AS160/GLUT4 signaling pathway.