The Chinese herbal medicine FTZ attenuates insulin resistance via IRS1 and PI3K in vitro and in rats with metabolic synd
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RESEARCH
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The Chinese herbal medicine FTZ attenuates insulin resistance via IRS1 and PI3K in vitro and in rats with metabolic syndrome Xuguang Hu†, Man Wang†, Weijian Bei, Zongyu Han and Jiao Guo*
Abstract 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, has been used to relieve hyperlipidemia, atherosclerosis and other symptoms associated with metabolic disorders in the clinic. Methods: To evaluate the effect of FTZ on insulin resistance, HepG2 cells were induced with high insulin as a model of insulin resistance and treated with FTZ at one of three dosages. Next, the levels of glucose content, insulin receptor substrate1 (IRS1) protein expression and phosphatidylinositol 3-kinase (PI3K) subunit p85 mRNA expression were measured. Alternatively, MS was induced in rats via gavage feeding of a high-fat diet for four consecutive weeks followed by administration of FTZ for eight consecutive weeks. Body weight and the plasma levels of lipids, insulin and glucose were evaluated. Finally, the expression of PI3K p85 mRNA in adipose tissue of rats was measured. Results: Our results revealed that FTZ attenuated glucose content and up-regulated the expression of PI3K p85 mRNA and IRS1 protein in insulin-resistant HepG2 cells in vitro. Moreover, FTZ reduced body weight and the plasma concentrations of triacylglycerol, cholesterol, fasting glucose and insulin in insulin resistant MS rats. FTZ also elevated the expression of PI3K p85 mRNA in the adipose tissues of MS rats. Conclusion: FTZ attenuated MS symptoms by decreasing the plasma levels of glucose and lipids. The underlying mechanism was attenuation of the reduced expression of PI3K p85 mRNA and IRS1 protein in both insulin-resistant HepG2 cells and MS rats. Keywords: Metabolic syndrome, Insulin resistance, Fu Fang Zhen Zhu Tiao Zhi formula (FTZ)
Background Reaven noted that dyslipidemia, hypertension and hypertriglyceridemia often occurred together [1]. Consequently, this author proposed the concept of X Syndrome, regarding insulin resistance as the primary characteristic of X Syndrome. Based on the association of X syndrome with a variety of metabolic diseases, Zimmet et al. defined its symptoms as metabolic syndrome (MS). MS is related to excessive energy intake, a sedentary lifestyle, and * Correspondence: [email protected] † Equal contributors Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Level 3 Lab of Lipid Metabolism SATCM, Guangdong TCM key laboratory for metabolic diseases, Guangdong Pharmaceutical University, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China
multiple genetic factors [2]. Many studies have demonstrated that patients with MS displayed an increased risk of developing diabetes, cardiovascular disease and other diseases. Insulin resistance (IR) has been suggested as the common pathophysiological basis of MS. Because there is no eut
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