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The Molecular Mechanism and Effect of Different Compatibility Proportion of Jiaotai Pills on Treating Type 2 Diabetes Mellitus in Rats

Author: WangJianHong
Tutor: LuFuEr
School: Huazhong University of Science and Technology
Course: Traditional Chinese Medicine
Keywords: Jiaotai Pills Compatibility Type 2 diabetes mellitus Rats Insulin signal transduction pathway
CLC: R285.5
Type: Master's thesis
Year: 2010
Downloads: 37
Quote: 0
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Abstract


Effect of different compatibility proportion of Jiaotai Pills on treating type 2 diabetes mellitus in ratsObjectiveTo study the effect of different compatibility proportion of Jiaotai Pills on treating type 2 diabetes mellitus (T2DM) in rats.MethodsThe model of type 2 diabetes mellitus in rats was established by injection of streptozotocin from tail vein and feeding with high fat and high caloric diet. Diabetic rats were randomly divided into model group, Jiaotai Pills group 1 (Rhizoma Coptidis : cinnamon=2:1), Jiaotai Pills group 2 (Rhizoma Coptidis : cinnamon=4:1), Jiaotai Pills group 3 (Rhizoma Coptidis : cinnamon=10:1) and metformin group. Rats in different treatment groups were given by corresponding therapy from gastric tube. Meanwhile normal animal was set as normal control group. Body weight, oral glucose tolerance test (OGTT), blood lipids level including total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), plasma levels of free fatty acid (FFA) and adiponectin, plasma liver enzymes activity(ALT、AST、AKP、γ-GT)and pathological results of liver tissue were determined at the eighth week end after experiment.ResultsBody weight, fasting plasma glucose (FPG), postpradial plasma glucose at one hour (PG-1h), postpradial blood glucose at two hour (PG-2h), plasma levels of TC, TG, LDL-C, FFA and liver enzymes activity were all increased in rats of model group, compared with those in normal control group. Plasma levels of HDL-C and adiponectin were decreased in model group (P<0.01). Fatty degeneration of hepatocytes was apparent in liver tissues in rats of model group. Compared with model group, the results of OGTT, blood lipid levels and liver enzymes activity were improved, while the levels of HDL-C and adiponectin were increased in rats of different treatment groups (P<0.05 or P<0.01). Meanwhile fatty degeneration of hepatocytes was improved in liver tissues in rats of different treatment groups. Compared with metformin group, plasma level of HDL-C was elevated while AKP andγ-GT were decreased significantly in rats of Jiaotai Pills group 1 (P<0.05),γ-GT level was decreased significantly in rats of Jiaotai Pills group 2 (P<0.05), AST, AKP andγ-GT levels were decreased significantly in rats of Jiaotai Pills group 3 (P<0.05). Compared with Jiaotai Pills group 1, plasma levels of HDL-C was decreased while AKP levels was elevated significantly in rats of Jiaotai Pills group 2, but HDL-C was decreased in rats of Jiaotai Pills group 3 (P<0.05).ConclusionIt is suggested that the different compatibility proportion of Jiaotai Pills are effective on treating type 2 diabetes mellitus in rats. The effect of Jiaotai Pills group 1 is better than that of other therapy groups. The effect of Jiaotai Pills with different compatibility proportion on different protein expressions involved in insulin signal transduction pathway in skeletal muscle tissues of type 2 diabetic ratsObjectiveTo explore the effect of Jiaotai Pills with different compatibility proportion on different protein expressions involved in insulin signal transduction pathway in skeletal muscle of type 2 diabetic rats.MethodsAnimal models of type 2 diabetes mellitus (T2DM) were established by intravenous injection of small dose of streptozotoein plus high fat and high caloric laboratory chow. Diabetic rats were randomly divided into model group, Jiaotai Pills group 1 hizoma Coptidis : cinnamon=2:1), Jiaotai Pills group 2 (Rhizoma Coptidis : cinnamon=4:1) , Jiaotai Pills group 3 (Rhizoma Coptidis : cinnamon=10:1) and metformin group. Correspond therapies were administered to the different treatment groups. Meanwhile, a normal control group was established. Eight weeks later, body weight, oral glucose tolerance test (OGTT) and fasting serum insulin (FINS) levels were detected. The expressions of insulin receptor substrate-1 (IRS-1) and its serine phosphorylation level, tyrosine phosphorylation level, InsRβsubunit and its tyrosine phosphorylation level, phosphatidylinositol-3-kinase (PI-3K) p85 subunit, glucose transporter 4 (GLUT4) in skeletal muscle tissues were determined by Western blot.ResultsCompared with the normal group, plasma glucose, FINS and HOMA-IR levels were increased in rats of model group with the decrease of the tyrosine phosphorylation of IRS-1, InsRβ, expressions of IRS-1, InsRβ, PI-3K p85, GLUT4 and increase of serine phosphorylation of IRS-1 in skeletal muscle tissues (P<0.01, P<0.05). Compared with the model group, plasma glucose, FINS and HOMA-IR levels were decreased in rats of different treatment groups with the significant increase of the tyrosine phosphorylation of IRS-1, InsRβ, expressions of IRS-1, InsRβ, PI-3K p85, GLUT4 and the decrease of IRS-1 ser307 in skeletal muscle tissues (P<0.01, P<0.05). Compared with metformin group, the IRS-1 tyrosine phosphorylation level of Jiaotai Pills group 1and the expressions of GLUT4 proteins of Jiaotai Pills group 3 in skeletal muscle tissues in rats was significantly decreased (P<0.05) . Compared with other Jiaotai Pills groups, the expression of protein IRS-1, InsRβsubunit, GLUT4 and tyrosine phosphorylation level of IRS-1, InsRβsubunit in skeletal muscle tissues were increased, serine phosphorylation level of IRS-1 was reduced significantly in rats of Jiaotai Pills group 1 (P<0.05).ConclusionJiaotai Pills with different compatibility proportion are effective on treating type 2 diabetic rats. The mechanism may be associated with the increased expression of protein IRS-1, InsRβsubunit, PI-3K p85 subunit, GLUT4 and tyrosine phosphorylation level of IRS-1, InsRβsubunit, and the reduced state of serine phosphorylation level of IRS-1 in skeletal muscle tissues.

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