2型糖尿病模型大鼠肝脂代谢相关基因的筛选及生物信息学分析（英文）

发布时间：2018-02-09 10:42

本文关键词： 型糖尿病肝脂肪代谢胰岛素抵抗基因表达发病机制　出处：《中国生物化学与分子生物学报》2017年07期 　论文类型：期刊论文

【摘要】：肝的脂肪代谢异常和胰岛素抵抗(insulin resistance,IR)对促进2型糖尿病(type 2 diabetes mellitus,T2DM)的发生与发展具有显著影响。但此过程复杂,参与调控基因目前尚未完全清楚。有研究表明,脂肪酸分解、氨基酸代谢、肝糖原合成等生物过程对糖尿病的形成具有促进作用。为了阐明这一调控机制,本文通过基因芯片技术研究GK(Goto-Kakizaki)大鼠和WKY(Wistar-Kyoto)大鼠肝差异基因对肝的脂肪代谢和胰岛素抵抗的影响,探讨可引起2型糖尿病发病的分子机制。从基因表达数据库(GEO)获取GSE13271基因表达谱,并对原始数据进行标准化处理。通过GO(Gene Ontology)、KEGG(Kyoto Encyclopedia of Genes and Genomes enrichment)、String和Cytoscape软件对差异表达基因进行功能分析。结果从GK和WKY大鼠中分别获得179和278个差异基因,同时从排名前10的路径中筛选出21个差异基因(Aldh1a1,Cyp2c22,Fabp2,Fabp7,Cyp4a3,Acot1,Acot2,Hsd17b2,Ech1,Hmgcl,Bdh1,Crot,Pex11a,Cpt1a,Hadhb,Gda,Elovl2,Prodh,Agpat3,Sardh,Pigu),将这些基因与前10个的GO term取交集。最终得到10个显著差异基因(Aldh1a1,Fabp2,Acot1,Acot2,Ech1,Hmgcl,Bdh1,Crot,Cpt1a,Hadhb),功能分析结果显示,肝组织相关基因通过一系列生物过程对肝的脂肪代谢和胰岛素抵抗产生调节作用,从而也为临床糖尿病的治疗以及新作用靶点的发现提供更多参考依据。
[Abstract]:Abnormal lipid metabolism in liver and insulin resistance IRR have a significant effect on the development and development of type 2 diabetes mellitus type 2 diabetes mellitusus T2DM.However, the process is complex and the genes involved in regulation are not completely clear. Some studies have shown that fatty acid catabolism. Amino acid metabolism, liver glycogen synthesis and other biological processes promote the formation of diabetes mellitus. In this paper, the effects of liver differential genes on fat metabolism and insulin resistance in the liver of GKG Goto-Kakizaki and WKYY Wistar Kyoto rats were studied by gene chip technique, and the molecular mechanism of the pathogenesis of type 2 diabetes was explored. The GSE13271 gene expression profile was obtained from gene expression database. The differential expression genes were analyzed by GO(Gene Ontology Encyclopedia of Genes and Genomes chromosome string and Cytoscape software. Results 179 and 278 differentially expressed genes were obtained from GK and WKY rats, respectively. At the same time, 21 differentially expressed genes, Aldh1a1, Cyp2c22, Fabp2Cyp4a3, Acot1, Acot2Acot2Acot2Acot2Acot2Acot2Acot1, HmgclclBdh1, CrotPex11aCpt1a, HadhbGlovl2Prodhlprodh2Prodh2Sardh term, were screened from the top 10 genes. Finally, 10 distinct genes, Aldh1a, Acot1a, Acot2Acot2Ech1Ech1hmchlhlhchlt1, BhhltCp1t1a, have been obtained. The results show that the results show that the results show that the results show that the results show that the results show that these genes are intersected with the term of the former 10 genes. Finally, the results of the analysis show that there are 10 significant differences between the two genes. Liver tissue related genes regulate liver fat metabolism and insulin resistance through a series of biological processes, thus providing more references for the treatment of diabetes mellitus and the discovery of new targets.
【作者单位】：安徽中医药大学研究生院;安徽中医药大学第一附属医院国家中药制剂三级实验室;
【基金】：Supported by State Administration of Traditional Chinese Medicine Clinical Research Base for the Construction of the Second Batch of Special Research Projects(No.JDZX2015126) Anhui University of Chinese Medicine Youth Science Research Foundation(No.2014qn018)~~
【分类号】：R-332;R587.1

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