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Proteomic Study on the New Potential Mechanism and Biomarkers of Diabetes

机译:糖尿病新潜在机制和生物标志物的蛋白质组学研究

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Purpose Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia. So far, the pathogenesis of diabetes has not been fully elucidated. Identifying new potential molecule mechanisms and biomarkers in this process could contribute to the understanding of pathophysiology. Experimental design Proteomic changes in the liver of type 2 diabetic mice ( n = 6) and normal mice ( n = 6) are studied. Triplicate experiments are carried out for each sample. Results A total of 15 differentially expressed proteins (DEP S ) are identified and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicates that DEP S mainly involved two inflammatory pathways: glutathione metabolic pathway and the arachidonic acid metabolic pathway. The core of protein–protein interaction is the tumor necrosis factor inflammatory pathway, indicating the connection between inflammation and diabetes. Ten out of fifteen gene transcript levels are consistent with proteomics by quantitative RT‐PCR validation. The transcriptional levels of OAT (ornithine aminotransferase) and fructose‐1,6‐bisphosphatase1 (FBP1) were significantly increased, whereas fatty acid binding protein 5 (FABP5) and ef‐2 transcription levels decreased significantly. In addition, western blotting results showed that the expression of OAT and FBP protein increased significantly in the diabetes group, while elongation factor 2 decreased significantly and FABP do not have significant difference in the diabetes group. Conclusions and clinical relevance Taken together, the present exploratory liver proteomic analysis might be seen as an important starting point for studies targeting specific liver proteins aimed at the implementation of new biomarkers for the early detection of type 2 diabetes mellitus‐related potential mechanisms, hoping to provide biomarkers and clinical therapeutic targets of type 2 diabetes mellitus.
机译:目的糖尿病是一种代谢疾病,其特征在于慢性高血糖。到目前为止,糖尿病的发病机制尚未完全阐明。鉴定该过程中的新潜在分子机制和生物标志物可以有助于理解病理生理学。研究了2型糖尿病小鼠(n = 6)和正常小鼠(n = 6)的肝脏的实验设计蛋白质组学变化。对每个样品进行三份实验。结果鉴定了总共15种差异表达的蛋白质(DEP S),并且基因的京都植物和基因组富集分析表明,DEP S主要涉及两种炎症途径:谷胱甘肽代谢途径和花生酸代谢途径。蛋白质 - 蛋白质相互作用的核心是肿瘤坏死因子炎症途径,表明炎症与糖尿病之间的联系。十五个基因转录水平中的十个与蛋白质组学通过定量的RT-PCR验证一致。燕麦(鸟氨酸氨基转移酶)和果糖-1,6-双磷酸酶1(FBP1)的转录水平显着增加,而脂肪酸结合蛋白5(FABP5)和EF-2转录水平显着降低。此外,Western印迹结果表明,糖尿病组燕麦和FBP蛋白的表达显着增加,而延长因子2显着下降,造粒糖尿病组没有显着差异。结论和临床相关性,目前的探索性肝蛋白质组学分析可能被视为针对靶向特定肝蛋白的研究的重要起点,旨在实施新的生物标志物,以便早期检测2型糖尿病相关潜在机制的潜在机制,希望提供2型糖尿病的生物标志物和临床治疗靶标。

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