Research Of FTZ On The Function And Mechanism Of Insulin Resistance

Background:Insulin resistance plays an important role in the development of metabolic syndrome(MS). Fu Fang Zhen Zhu Tiao Zhi formula (FTZ), a Chinese medicinal decoction, hasbeen used to relieve hyperlipidemia, atherosclerosis and other symptoms associatedwith metabolic disorders in the clinic.Objective:In order to explore the mechanism of Fu Fang Zhen Zhu Tiao Zhi formula (FTZ) andsupport experimental evidence for further development and clinical application,observe the effect of FTZ on insulin-resistant HepG2cells and MS rats，and theexpression of phosphatidylinositol3-kinase (PI-3K) p85subunit and insulin receptorsubstrate1(IRS1) protein.Methods：To evaluate the effect of FTZ on insulin resistance, HepG2cells were induced withhigh insulin as a model of insulin resistance and treated with FTZ at one of threedosages. Next, the levels of glucose content, insulin receptor substrate1(IRS1) proteinexpression and phosphatidylinositol3-kinase (PI3K) subunit p85mRNA expressionwere measured. Alternatively,60SD rats were randomly divided into6groups:normal control rats, model rats, aspirin positive control rats (200mg/kg), FTZ high(6g/kg), medium (3g/kg), low (1.5g/kg) dosage rats. MS was induced in rats viagavage feeding of a high-fat diet for four consecutive weeks followed byadministration of FTZ for eight consecutive weeks. Body weight and the plasmalevels of lipids, insulin and glucose were evaluated. Finally, the expression of PI3K p85mRNA in adipose tissue of rats was measured.Results：Our results revealed that FTZ attenuated glucose content and up-regulated theexpression of PI3K p85mRNA and IRS1protein in insulin-resistant HepG2cells invitro. Moreover, FTZ reduced body weight and the plasma concentrations oftriacylglycerol, cholesterol, fasting glucose and insulin in insulin resistant MS rats.FTZ also elevated the expression of PI3K p85mRNA in the adipose tissues of MSrats.Conclusions：FTZ attenuated MS symptoms by decreasing the plasma levels of glucose and lipids.The underlying mechanism was attenuation of the reduced expression of PI3K p85mRNA and IRS1protein in both insulin-resistant HepG2cells and MS rats.