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A Primary Study Of The Induction Of DEHP On Type 2 Diabetes Mellitus Mice

Posted on:2012-11-17Degree:MasterType:Thesis
Country:ChinaCandidate:J WangFull Text:PDF
GTID:2154330335468711Subject:Biochemistry and molecular
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Diabetes mellitus, often simply referred to as diabetes—is a group of metabolic diseases characterized by high blood sugar (glucose) levels, that result from defects in insulin secretion, or action, or both. This high blood sugar produces the classical symptoms of polyuria (frequent urination), polydipsia (increased thirst) and polyphagia (increased hunger). Then causing a sugar, fat and protein metabolism disorders and gradually cause the other organs injury and dysfunction. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a lifetime. Diabetes is listed as one after the cardiovascular disease and cancer to be the third-largest stubborn disease. Recently, China has become a world diabetic patients most populous country. Type 2 diabetes is the most common type. Di-(2-ethylhexyl) phthalate (DEHP) is one of the phthalate esters, which was most widely used in the plastic industry as a very important plasticizer. Nowadays the research of the toxicity of DEHP is a hot and difficult spot in the field of hygienical and had been taken great notice over all the world.A epidemiological studies researched by the US Stahlhut found that there is a correlation exists between the diabetes and phthalic acid esters. However, it yet dosn't have a relevant animal models, and the mechanism of the effect due to DEHP still need a further research. In my study, the purpose is to explore the DEHP-induced diabetes and the pathogenesis of diabetes and the role of genotoxicity, which is of great significance to understand the toxicity of DEHP. So, I choose the DEHP exposed Balb/C mice with a high fat diet raised, and then get a STZ direct injection to infect the type 2 diabetes model.1. The establishment of DEHP-induced diabetes mice modelAfter 3 to 4 days adaptable feeding, Mice were randomly divided into 8 groups. The singular groups feed with high-fat diet, and the array groups feed ordinary diet(including 0 group). Every day 0 group and 1 group get a oral exposure of saline,2 group and 3 group irrigate lOmg/kg/d DEHP,4 group and 5 group with 50mg/kg/d DEHP irrigation,6 group and 7group infected 250mg/kg/d DEHP. After 3 weeks exposure, fasting blood were tested, and the next day singular groups were intraperitoneal injected STZ solution weight 100mg/kg(the control groups inject citrate buffer), blood sugar Measured another week, and the a second STZ injection again with a concentration of 80mg/kg.7days later, diabetes mice appear, and no longer STZ injection, then get a DEHP exposure for another 3 weeks. Fasting blood sugar valued every week, after death, many index were tested, such as the oxidative damage on liver, pancreas, and kidney biopsy, and serum insulin content, etc.2. The direct and indirect effects within the DEHP induced diabetesBy using the differentiated model for either the direct or indirect effects of DEHP on diabetes, the present study made a preliminary view on the possible mechanisms of DEHP-induced diabetes. The results showed that DEHP as a kind of environmental factors, can really impact on the development of diabetes. Combined with the experimental index, DEHP exposure groups can infected organism produces corresponding the oxidative damage and various viscera toxic effects. These stimulus led a certain differences when compared with the control group, and this difference related with the DEHP concentration. However, the toxicity of DEHP cannot directly induce diabetes, and in the joint action of the modeling groups, DEHP played obvious influence. This can be confirmed by the symptoms of diabetes performance and insulin levels. In addition the results of oxidative damage index also reflect the DEHP auxiliary effect, and showed that DEHP isn't entirely directly the influence mechanism of diabetes through its oxidative damage effect, there must be some other mediated access, such as reproductive toxicity (testosterone impact), proinflammatory effect et al., to make the diabetes developed much more easily. This corollary need a further study of the DEHP modeling group and separate DEHP exposure mice with the related cell factors and diabetes susceptibility genes about insulin resistance and various body on the insulin action pathways.
Keywords/Search Tags:diabetes, type 2 diabetes model, insulin, oxidatie stress, DEHP, blood sugar, oxidative damage
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