"xin Open Bitter Drop Method" Intervention Irs - 2 / Pi3 - K Pathway Mediated Compatibility Mechanism Of Hepatic Insulin Resistance In Type 2 Diabetes Mellitus

Diabetes is a disorder of glucose metabolism as the main clinical manife-stations of the clinical syndrome, causing by genetic and environmental factors. The incidence of diabetes has increased year by year in the world, which has been classified as the third major disease after Cardiovascular and cerebrovascular diseases and tumors. The harm of diabetes is a variety of chronic complications on the basis of atherosclerosis and microvascular disease for human health, for example diabetic cardiopathy、diabetic retinopathy、diabetic nephropathy、diabetic neuropathy、diabetic gangrene. More than ninety percent of diabetic patients are type2diabetes mellitus (T2DM).The central links of type2diabetes mellitus are insulin resistance and pancreaticβ cell dysfunction. Prevention of diabetes can be achieved through reducing hepatic insulin resistance and protecting the function of pancreatic β cell. It has been paid attention in recent years, also provided a new way to treating diabetes.This article is divided into parts, the first part of literature review divided into two reviews-the traditional Chinese medicine and western medicine review. The traditional Chinese medicine review is including the nonaggressive understanding of type2diabetes mellitus, the etiology and pathogenesis, differentiation of symptoms and signs, the discussion of therapeutic principle. Western medicine review is including summary and discussion about the factors of hepatic insulin resistance and pancreatic β cell dysfunction, the research progress of pancreatic (3cell protection.The second part is animal experimental study:Objective:Investigating the mechanism of "Xinkaikujiang method" to interfere with the hepatic insulin resistance of type2diabetes mellitus through IRS-2/PI3-K pathwaymethod:By high energy diet on the establishment of transgenic Kkay mice model of type2diabetes mellitus, mice in meeting the requirements by fasting plasma glucose levels were randomly divided into five groups, namely XinKai group, KuJiang group, XinKaiKuJiang group, Rosiglitazone group, the model group. It had been set up C57BL/6J mice as normal control group which had gene homology with Kkay mice. Each group mice were measured fasting plasma glucose, blood lipids, insulin concent rat ion,liver glycogen and lipid detection of liver tissue after continuously intragastric administration four weeks.At the same time, we observe changes of liver pathology by light microscopy. In the level of protein and gene, we observe the effectiveness of Xinkaikujiangfang and its decomposed formulas to the expresstion of the key molecules, for example ISR-2,3,4, PI3K and their phosphorylated forms, InsR, by using Western blot, Realtime-PCR,etc. Results:XinKaiKuJiang fang and KuJiang fang can significantly reduce the blood glucose of the type2diabetes mellitus model-Kkay mice, and enhance insulin sensitivity. They are significantly different from the model group (P<0.05). XinKaiKuJiang fang can also reduce the levels of triglycerides of blood lipids and hepatic lipid, enhance the protein expression of key molecules, for example ISR-2,3,4, PI3K and their phosphorylated forms, InsR. They are significantly statistical difference among these groups (P<0.05).Conclusion:1. KuJiang fang can significantly reduce the blood glucose of the type2diabetes mellitus model-Kkay mice. XinKaiKuJiang fang and its decomposed formulas can lower serum insulin concentration,enhance insulin sensitivity, higher hepatic glycogen content and reduce hepatic insulin resistance. The effect of XinKaiKuJiang fang is better than decomposed formular. It expounds that compatibility of XinKaiKuJiang fang is valid.2. XinKaiKuJiang fang and its decomposed formulas could restore the balance of positive regulation and negative regulation of insulin receptor substrate through enhancing protein expression of insulin receptor substrate-2and its phosphorylated form, inhibiting protein expression of insulin receptor substrate-3,4in the liver cells. The effect of XinKaiKuJiang fang is better than decomposed formular.3. XinKaiKuJiang fang can enhance the mRNA expression of PI3-K in order to reduce insulin resistance. XinKai fang and KuJiang fang have not obvious effect.4. XinKaiKuJiang fang can lower the levels of triglycerides of blood lipids and he pat ic lipid, improve the state of lipid metabolism disorder, which can further reduce body insulin resistance. The effect is not obvious for simple application of XinKai fang or KuJiang fang.