食蟹猴2型糖尿病模型发病进程的分子机制研究

Type 2 diabetes mellitus (T2DM) and its syndromes are spreading rapidly, which has become a serious threat to human health in the world. Due to absence of the ideal T2DM animal models which can simulate human T2DM onset and progress, the molecular pathogenesis of the progress of T2DM has not yet been elucidated. The cynomolgus T2DM model can preferably simulate human T2DM onset and progress. After completing the following researches, cynomolgus genome sequencing, cynomolgus T2DM model constructing, differentially expressed miRNA in the blood of cynomolgus T2DM model and susceptible SNP marker screened in T2DM cynomolgus, the project is plan to construct the cynomolgus T2DM model with the susceptible SNP markers and so on, at the same time, the physiological parameters (fasting blood glucose, glycosylated hemoglobin and so on) are long-term tracked and monitored in the progress of cynomolgus T2DM, and the genome-wide microRNA and the the target transcript and protein expressing profile in the progress of cynomolgus T2DM are also analyzed and verified by the next generation sequencing technology to reveal the molecular pathogenesis of T2DM progression systematically and comprehensively, to elucidate the pathogenesis and causalities of 1 differentially expressed miRNA and its signaling pathway in T2DM, which will provide theoretical basis for target selection and new drug development for T2DM.

2型糖尿病（T2DM）的迅速蔓延已成为严重威胁人类健康的世界性难题。因缺乏能模拟人T2DM发病进程的理想的疾病模型，T2DM发病进程的分子机制至今尚未阐明。食蟹猴T2DM模型能较好模拟人T2DM发病进程，因此本项目在完成食蟹猴全基因组测序、食蟹猴T2DM模型构建、T2DM食蟹猴血液中差异表达miRNA以及筛到食蟹猴T2DM易感SNP标记等工作基础上，利用易感SNP标记等方法来制备食蟹猴T2DM模型，长期跟踪监测食蟹猴T2DM发病进程中总胆固醇等多项生理指标，采用二代基因组测序等技术在全基因组范围内分析和验证T2DM发病进程中miRNA及靶基因的mRNA和蛋白的表达规律，深入揭示T2DM发病进程的分子机制，诠释1个差异表达的miRNA及其信号通路在T2DM发病进程的分子机制，为T2DM治疗靶标的选择和新药研发提供理论依据。

围绕着2型糖尿病进行系统生物学（包括生物信息挖掘和我们自己的测序等）的研究，深挖靶标候选基因和生物标志物，找到LYN候选基因和microRNA-182生物标志物等。在journal of diabetes research (IF=3.5)发表2篇论文，比较医学杂志发表1篇，详情请见附件。

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