Metz Thomas O, Jacobs Jon M, Gritsenko Marina A, Fontès Ghislaine, Qian Wei-Jun, Camp David G, Poitout Vincent, Smith Richard D
Biological Science Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington, USA.
J Proteome Res. 2006 Dec;5(12):3345-54. doi: 10.1021/pr060322n.
The pancreatic beta-cell plays a central role in the maintenance of glucose homeostasis and in the pathogenesis of both type 1 and type 2 diabetes mellitus. Elucidation of the insulin secretory defects observed in diabetes first requires a better understanding of the complex mechanisms regulating insulin secretion, which are only partly understood. While there have been reports detailing proteomic analyses of islet cell lines or isolated rodent islets, the information gained is not always applicable to humans. Therefore, definition of the human islet proteome could contribute to a better understanding of islet biology and lead to more effective treatment strategies. We have applied a two-dimensional LC-MS/MS-based analysis to the characterization of the human islet proteome, resulting in the confident identification of 29,021 different tryptic peptides covering 3365 proteins (> or =2 unique peptide identifications per protein). As expected, the three major islet hormones (insulin, glucagon, and somatostatin) were detected, as well as various beta-cell enriched secretory products, ion channels, and transcription factors. In addition, significant proteome coverage of metabolic enzymes and cellular pathways was observed, including the integrin signaling cascade and the MAP kinase, NF-kappa beta, and JAK/STAT pathways. The resulting peptide reference library provides a resource for future higher throughput and quantitative studies of islet biology.
胰腺β细胞在维持血糖稳态以及1型和2型糖尿病的发病机制中起着核心作用。要阐明糖尿病中观察到的胰岛素分泌缺陷，首先需要更好地理解调节胰岛素分泌的复杂机制，而目前对这些机制的了解还只是部分的。虽然已有报告详细描述了胰岛细胞系或分离的啮齿动物胰岛的蛋白质组学分析，但所获得的信息并不总是适用于人类。因此，定义人类胰岛蛋白质组有助于更好地理解胰岛生物学，并带来更有效的治疗策略。我们应用基于二维液相色谱-串联质谱的分析方法来表征人类胰岛蛋白质组，从而可靠地鉴定出29021种不同的胰蛋白酶肽段，覆盖3365种蛋白质（每种蛋白质至少有2个独特的肽段鉴定）。正如预期的那样，检测到了三种主要的胰岛激素（胰岛素、胰高血糖素和生长抑素），以及各种富含β细胞的分泌产物、离子通道和转录因子。此外，还观察到代谢酶和细胞途径在蛋白质组中有显著覆盖，包括整合素信号级联以及丝裂原活化蛋白激酶、核因子κB和JAK/STAT途径。所得的肽段参考文库为未来对胰岛生物学进行更高通量和定量研究提供了资源。
