厄贝沙坦对高血压合并2型糖尿病大鼠胰岛素抵抗IRS-1/PI3K/GLUT4信号通路的影响

Effect of irbesartan on insulin resistance IRS-1/PI3K/GLUT4 signaling pathway in rats with hypertension and type 2 diabetes mellitus

目的探讨厄贝沙坦对高血压合并2型糖尿病(T2DM)大鼠胰岛素抵抗的影响及其作用。方法自发性高血压大鼠(SHR)采用高糖高脂饮食联合链脲佐菌素(STZ)建立T2DM模型,随机分为模型组、厄贝沙坦低、高剂量组。以正常大鼠作为对照组。厄贝沙坦低、高剂量组每日分别按30、60 mg/kg剂量灌服厄贝沙坦,对照组和模型组灌服等量生理盐水。测量大鼠收缩压(SBP)、空腹血糖(FBG)、胰岛素抵抗模型评估指数(HOMA-IR)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇(-3)激酶p85亚基(PI3Kp85)、蛋白激酶B(AKT)、磷酸化蛋白(p-AKT)及葡萄糖转运蛋白4(GLUT4)的表达。结果与对照组相比,模型组SBP、FBG、FINS和HOMA-IR升高(P<0.05),IRS-1、PI3Kp85、p-AKT和GLUT4降低(P<0.05);与模型组相比,厄贝沙坦低、高剂量上述指标均发生逆转(P<0.05)。结论厄贝沙坦可通过IRS-1/PI3K/GLUT4信号通路改善高血压合并T2DM大鼠胰岛素抵抗。

Objective To investigate the effect of irbesartan on insulin resistance in hypertensive rats with type 2 diabetes mellitus(T2DM).Methods Spontaneously hypertensive rats(SHR)were randomly divided into a model group,an irbesartan low dose group and an irbesartan high dose group.Normal rats were used as control group.Irbesartan was administered daily at 30 and 60 mg/kg in the low and high dose groups,while the same amount of normal saline was performed in the control group and model group.Systolic blood pressure(SBP),fasting blood glucose(FBG),insulin resistance model evaluation index(HOMA-IR),insulin receptor substrate-1(IRS-1),phosphatidylinositol(-3)kinase P85 subunit(PI3Kp85),protein kinase B(AKT),phosphorylated protein(p-AKT),and glucose transporter 4(GLUT4)were measured in rats.Results Compared with the control group,SBP,FBG,FINS and HOMA-IR in the model group significantly increased(P<0.05),while IRS-1,PI3Kp85,P-Akt and GLUT4 significantly decreased(P<0.05).Compared with the model group,the above indicators were reversed in both the low and high dose irbesartan groups(P<0.05).Conclusions Irbesartan can improve insulin resistance in T2DM rats with hypertension through IRS-1/PI3K/GLUT4 signaling pathway.