Mechanism of losartan in improviing insulin resistance of type 2 diabetes mellitus in rats

doi:10.3969/j.issn.1002-7386.2018.11.001

Abstract：Objective To investigate the effects of ARB in improving the metabolic effects of insulin and effects on phosphorylation of IRS1 induced by insulin and transposition of GLUT4 , and to explore whether its action mechanism depends on the pathway of PI3K. Methods Forty four SD rats were randomly divided into normal control group ( n =20) and model group ( n =22). The rats normal control group were fed with standard diet,however,the rats in model group were fed with high-fat and high-carbohydrate diet together with streptozotocin ( STZ ) . The rats with fasting plasma glucose ( FPG )≥7. 8mmol/L and insulin resistance were regarded as type 2 diabetic models. The rats in normal control group were randomly subdivided into control group A ( n =10) and treatment group B ( n =10),and 20 diabetic rats were randomly divided into NIDDM group C ( n =10) and NIDDM treatment group D ( n =10). The rats in group B and group D were treated with losartan for 6 weeks while the rats in group A and group C were treated with equivalent volume of 0. 9％ sodium chloride solution. Six weeks later, the rats were weighted, blood samples were collected to record glucose and insulin levers for calculation of ISI ( insulin sensitivity index) . Then the rats were fasted overnight and anesthetized for fifteen minutes before insulin injection. skeletal muscle was quickly removed from hind legs and stored at 80℃. RT PCR was used to detect the expression levels of GLUT4,IRS1,PI3K and AKT mRNA. Results As compared with those in group A and B, the body weight in group C and D was significantly increased, moreover, the levels of FPG, FINS were also significantly increased, however, ISI was decreased significantly( P <0. 05). After intervention with losartan, as compared with that in group C, the body weight in group D was increased, but the levels of FPG and FINS were decreased, moreover ISI was significantly increased ( P <0. 05). As compared with those in group A and B, the expression levels of GLUT4 mRNA in group C and D were significantly decreased ( P <0. 05),however, there were no differences in the expression levels of IRS1,PI3K and AKT ( P >0. 05). After intervention with losartan, there were no difference in the expression levels of GLUT4 mRNA between group C and group D ( P >0. 05),moreover there were nosignificant differences in the expression levels of IRS1,PI3K and AKT between the two groups ( P >0. 05). In addition there were no difference in the expression levels of GLUT4 mRNA, IRS1,PI-3K and AKT between group A and group B ( P >0. 05). Conclusion The losartan can improve IR of diabetic rats, increase the expression levels of Ptyr-IRS1 and GLUT4, and the action mechanism may be correlated with nonPI3 kinase pathway.