The Metabonomic Study Of Huanglian Jiedu Decoction On Improving Insulin Resistance

Objective: Insulin resistance(IR) is the pathogenetic basis of Type 2 diabetes mellitus(T2DM), and the metabolic syndrome is also typically characterized by IR. The data show that the incidence of diabetes mellitus(DM) was 11.6% and it has great increase in recent years. Now DM is the third disease following cardiopathy and cancer. Therefore, it is significant to find out the drugs for DM treatment. Western medicine treatment is easy to induce drug resistance and adverse reactions because of its single therapeutic target.Traditional Chinese medicine(TCM) has good effect in treatment of DM for thousands of years of history. Its mechanism of action is multiplex, multifaceted and multi-target.Therefore, TCM have many advantages over the chemical drugs. Clinical practice proved that Huanglian Jiedu decoction(HJD) plays a certain role in the treatment of DM and in improving insulin resistance. Under the guidance of the theories of TCM, nuclear magnetic resonance(NMR)-based metabonomics was applied to study the treatment effect of HJD on improving insulin resistance on the whole, and to clarify the metabolic regulation mechanism. This research supplies useful basis for its clinical application.Methods: In this study, we collected the plasma, urine, feces, pancreatic tissue and brown adipose tissue samples of control group, IR model(100 g/L high fructose feeding),atorvastatin(10 mg/ kg) and HJD treatment group(3.175 g/kg). And then we did the metabonomic research and analysed the metabolic regulation of HJD, to screen out the potential metabolic markers and reveal the metabolic regulation mechanism of HJD in improving IR. At the same time, the blood biochemical parameters of rats were measured.Results: Biochemical determination results show that the IR index increased by fructose feeding, and it decreased after HJD treatment, with statistical significance. HJD can regulate the metabolic profiles of plasma, urine, feces, pancreas and brown adipose tissues of model rats, and make the metabolic characteristics tend to normal group.(1) HJD canreduce the contents of lipid, taurine, TMAO/betaine and glycine in the plasma which induced by high fructose feeding, and increase the level of lactate, alanine, private and glycerol.(2) HJD can also inhibit the increase of TMAO/betaine and creatine/creatinine in the urine samples which caused by IR, and elevate the level of α-ketoglutaric acid(α-KG),citrate, choline, phosphorylcholine/glycerophosphorylcholine(PC/GPC), taurine and hippurate, and return them to normal in the urine of rats.(3) HJD can decrease the level of alanine, n-butyrate and glutamate in the fecal extracts which induced by high fructose feeding, and increase the level of propionate, acetate, isobutyrate, succinate, taurine and glycerol.(4) HJD can also effectively inhibit the increase of trimetlylamine oxide(TMAO)/betaine, taurine, glycine and myo-inositol in pancreatic tissue extracts, and elevate the lactate, glutamate, choline and PC/GPC, and return them to normal.(5) In addition,HJD can reverse the increase of lactate, alanine, PC/GPC, taurine, creatine/creatinine and inosine in brown adipose tissue samples, and increase the level of lipid.Conclusion: In the dissertation, the research involves metabonomics and biochemical determination to ascertain the effect of HJD on improving IR. HJD can regulate the metabolism disorder of the plasma, urine, feces, pancreas and brown adipose tissues in IR rats, involving the glucolipid, amino acid and intestinal flora metabolism regulation. This revealed the metabolic regulation mechanism of HJD, suppling useful basis for clinical application.