小柯机器人

美国太平洋西北国家实验室生物科学处Thomas O. Metz和美国印第安纳大学医学院Raghavendra G. Mirmira.研究组合作，通过应激人胰岛的综合蛋白质组学分析，确定生长/分化因子15（GDF15）为1型糖尿病（T1D）干预的靶标。该研究于2020年1月9日发表于国际学术期刊《细胞—代谢》。

为了鉴定参与该过程的蛋白质，他们对用白介素-1β和干扰素-γ处理的人胰岛进行了全面的蛋白质组学研究，从而鉴定出11,324种蛋白质，经过处理之后其中387种蛋白受到显著调节。然后，他们检测了GDF15的功能，其功能被该处理抑制。他们发现GDF15的翻译在炎症过程中受阻，并且在T1D患者的胰岛中发生缺失。外源GDF15的添加抑制白细胞介素-1β+干扰素-γ诱导的人胰岛细胞凋亡。在NOD小鼠中，给予GDF15可使糖尿病的发病率降低53%。他们的方法为鉴定受细胞因子调节的人类胰岛蛋白提供了独特的资源，并有效地发现了T1D治疗的潜在靶标。

据悉，T1D是由β细胞加工性丧失引起的，该过程是由促炎性细胞因子信号传导传播的，破坏了促凋亡和抗凋亡蛋白之间的平衡。

附：英文原文

Title: Comprehensive Proteomics Analysis of Stressed Human Islets Identifies GDF15 as a Target for Type 1 Diabetes Intervention

Author: Ernesto S. Nakayasu, Farooq Syed, Sarah A. Tersey, Marina A. Gritsenko, Hugh D. Mitchell, Chi Yuet Chan, Ercument Dirice, Jean-Valery Turatsinze, Yi Cui, Rohit N. Kulkarni, Decio L. Eizirik, Wei-Jun Qian, Bobbie-Jo M. Webb-Robertson, Carmella Evans-Molina, Raghavendra G. Mirmira., Thomas O. Metz

Issue&Volume: January 9, 2020

Abstract: Type 1 diabetes (T1D) results from the progressive loss of β cells, a process propagatedby pro-inflammatory cytokine signaling that disrupts the balance between pro- andanti-apoptotic proteins. To identify proteins involved in this process, we performedcomprehensive proteomics of human pancreatic islets treated with interleukin-1β and interferon-γ,leading to the identification of 11,324 proteins, of which 387 were significantlyregulated by treatment. We then tested the function of growth/differentiation factor15 (GDF15), which was repressed by the treatment. We found that GDF15 translationwas blocked during inflammation, and it was depleted in islets from individuals withT1D. The addition of exogenous GDF15 inhibited interleukin-1β+interferon-γ-inducedapoptosis of human islets. Administration of GDF15 reduced by 53% the incidence ofdiabetes in NOD mice. Our approach provides a unique resource for the identificationof the human islet proteins regulated by cytokines and was effective in discoveringa potential target for T1D therapy.

DOI: 10.1016/j.cmet.2019.12.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30670-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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