联合多种质谱定量策略用于胰岛β细胞功能研究

项目名称： 联合多种质谱定量策略用于胰岛β细胞功能研究

项目编号： No.31300700

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 生物科学

项目作者： 程冬婉

作者单位： 中国科学院生物物理研究所

项目金额： 22万元

中文摘要： 糖尿病是世界流行的代谢性疾病，患病率逐年升高。胰岛β细胞是体内唯一分泌降血糖激素--胰岛素的细胞。对胰岛β细胞功能尤其是合成和分泌胰岛素的功能研究，对糖尿病的发病机制和诊断治疗起关键作用。近年来，液相色谱-质谱联用技术在蛋白质定量研究方面的能力被广泛关注，已发展出多种标记和检测策略，使定量蛋白质组学研究的准确性、灵敏度、特异性和通量均极大提高。本课题拟联合应用多反应监测质谱和高精度全扫描质谱定量手段，利用其高灵敏度、高通量、高精度、动态范围宽的特点，结合稳定同位素标记氨基酸细胞培养技术，对糖尿病相关模型小鼠胰岛β细胞在不同刺激条件下合成和分泌胰岛素的动态过程、作为调控通路集合中心的胰岛素囊泡（DCV）中关键蛋白的动态变化、以及对β细胞功能至关重要的胰岛素受体信号通路关键蛋白的动态调控进行多方位的分析检测，以期阐述糖尿病及相关基因的分子机制，对糖尿病的发病机理和潜在治疗靶点提供指导意义。

中文关键词： 质谱；定量；胰岛β细胞；；

英文摘要： Diabetes is one of the most common metabolic diseases in the world, the prevalence of which increased year by year. Pancreatic islet β-cell is the only cell type in vivo which secretes the hypoglycemic hormone--insulin. The studys in β-cell function, especially the function of synthesis and secretion of insulin, play a key role in pathogenesis and treatment of diabetes mellitus. In recent years, the property of liquid chromatography - mass spectrometry teqhnology in protein quantitative research has been widespread concerned. A vairous of labeling and measureing strategies has been developed. These strategies enhance greatly the accuracy, sensitivity, specificity, and wide dynamic range of quantitative proteomics study. The project designs to apply the quantitative strategies of multiple reaction monitoring mass spectrometry and high-precision full-scan mass spectrometry, combined with stable isotope-labeled amino acid cell culture technology, to research the β-cell function of diabetes-related mouse model. Experiments are performed to detect the dynamic processing of synthesis and secretion of insulin, the dynamic changes of key proteins in insulin granules (DCV), as well as the dynamic regulation of key proteins in insulin receptor signaling pathway under different stimulation conditions. Hoping to explain th

英文关键词： Mass Spectrometry；Quantitative；Pancreatic Islet Beta Cell；；