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Association Between Mitochondrial DNA 16189 (Tâ†'C Transition) Variation And Ability Of Islet β-cell Excretion And Insulin Resistance

Posted on:2005-07-08Degree:MasterType:Thesis
Country:ChinaCandidate:Y YangFull Text:PDF
GTID:2144360125950417Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Presently, type 2 diabetes is regarded as a disease that is affected by environment and heredity. It is called hereditary susceptility disease. In 1980s, molecula biology technology had been applied to familial diabetic genetics, a suit of single genes about diabetes was found: insulin gene, insulin receptor gene and so on. In 1990s, a plenty of research findings had showed that mtDNA was one of the familial diabetic reasons and becamed a focus of diabetic field. Mitochondary is a place which store and supply energy for cells. It supplys the energy to life activity. So mitochondrial gene mutation indirectly affects all kinds of life forms depending on energy. MtDNA is the hereditary material half depended on kernel DNA. MtDNA is exposing in free radical inresulting from oxidative phosphorylation and deficient histine and deficient repairase so that mtDNA is apt to mutate. In addition to, mtDNA almost has no intervening sequence so that any mutation will affect domain and result in energy's dificiency. β-cell is defferent of others, its heterogy is higher than other cells, that is to say, mtDNA mutation aggregated inβ-cell andβ-cell should be apt to mutate. MtDNA mutation result in insulin deficiency by tricarboxylic acid cycle (TCA cycle) obstruction. TCA can produce enough energy to [ATP]/[ADP] concentration ratio's ascension. The acsension should result in K+ passageway's closing and Ca2+ passageway's opening and Ca2+ inflowing. Immediately Ca2+ inflowing can activate G-protein and all kinds of cascade reaction of kinase. So, insulin is excreted. MtDNA mutation can induce respiratory chain structural variation so as to change oxidative phosphorylation course (OXPHOS) to change the excreted function of β-cell normally. The mutation of mtDNA 3316, mtDNA 3243 A/G, mtDNA 3394 and mGTDH gene can induce obstruction of the energy producing or impair the β-cell resulting in the incline of excretory function. Insulin resistance and β-cell function deficiency is the basal pathogenesis of type 2 diabetes. MtDNA mutation affect not only β-cell function, but also insulin resistance. In muscle and lipid tissue glucose is used by energy consumption. So, the deficiency of energy can increase insulin resistance. In those vigorous tissues of glycometabolism such as liver and muscle, the impairment of the respiratory chain polypeptide structure impact not only OXPHOS, but also TCA. TCA impairment bring about the obstraction of acetyl coenzyme A (CoA) using to glycometobolism impact diabete with insulin resistance.Although lots of predisposing genes of type 2 diabetes have been inspected, the relationship between type 2 diabetes and predisposing genes seldom was explained. This study will explain the relationship between type 2 diabetes and mtDNA 16189T/C (T-C transition) on the level of β-cell function deficiency and insulin resistance. The number of case group come from type 2 diabetic patients in the second clinical medical college of Jilin University from Mary 2002 to April 2003. The member of control group is composed of the husbands or wives of the base and the patients coming from surgerical department on the same time without diabetes and impairment glucose tolerance and familial history. All objects was compareable in years, gender. The taking of blood sample and the collection of data is completed by the same man so as to induce error. The datas and results of examination are filled into questionaire and conserved in computer. Some of the blood samples was used to exam clinical datas, others was conserved until taking DNA. We took DNA by the same of kit and disposed the PCR product by PCR-RELP technology. According to the results of gel elecrophosis, the base group was divided into viriation group and nonvariation group. Then the clinical datas was analyzed.The finding of research, the product of PCR is 229bp according with references. There are the sites of SNP that will be recognized by reseriction enzyme, So 166bp and 229bp can be got. The incidence rate of mtDNA 16189 T/C variation is 32...
Keywords/Search Tags:Type 2 diabetes, variation insulin resistance, β-cell, SNP, mtDNA genes
PDF Full Text Request
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