Crèvecoeur Inne, Rondas Dieter, Mathieu Chantal, Overbergh Lut
Laboratory for Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
Proteomics Clin Appl. 2015 Aug;9(7-8):755-66. doi: 10.1002/prca.201400135. Epub 2015 Mar 26.
Pancreatic beta-cells have a crucial role in the regulation of blood glucose homeostasis by the production and secretion of insulin. In type 1 diabetes (T1D), an autoimmune reaction against the beta-cells together with the presence of inflammatory cytokines and ROS in the islets leads to beta-cell dysfunction and death. This review gives an overview of proteomic studies that lead to better understanding of beta-cell functioning in T1D. Protein profiling of isolated islets and beta-cell lines in health and T1D contributed to the unraveling of pathways involved in cytokine-induced cell death. In addition, by studying the serological proteome of T1D patients, new biomarkers and beta-cell autoantigens were discovered, which may improve screening tests and follow-up of T1D development. Interestingly, an important role for PTMs was demonstrated in the generation of beta-cell autoantigens. To conclude, proteomic techniques are of indispensable value to improve the knowledge on beta-cell function in T1D and the search toward therapeutic targets.
胰腺β细胞通过胰岛素的产生和分泌在调节血糖稳态中发挥关键作用。在1型糖尿病(T1D)中,针对β细胞的自身免疫反应以及胰岛中炎性细胞因子和活性氧的存在会导致β细胞功能障碍和死亡。本综述概述了蛋白质组学研究,这些研究有助于更好地理解T1D中β细胞的功能。对健康和T1D状态下分离的胰岛及β细胞系进行蛋白质谱分析,有助于揭示细胞因子诱导的细胞死亡所涉及的途径。此外,通过研究T1D患者的血清蛋白质组,发现了新的生物标志物和β细胞自身抗原,这可能会改善T1D发展的筛查测试和随访。有趣的是,翻译后修饰(PTMs)在β细胞自身抗原的产生中显示出重要作用。总之,蛋白质组学技术对于增进对T1D中β细胞功能的了解以及寻找治疗靶点具有不可或缺的价值。