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通过网膜脂肪组织的蛋白质组学分析鉴定脂肪细胞质膜相关蛋白(APMAP)在妊娠期糖尿病中的新功能

Identification of a Novel Function of Adipocyte Plasma Membrane-Associated Protein (APMAP) in Gestational Diabetes Mellitus by Proteomic Analysis of Omental Adipose Tissue.

作者信息

Ma Yuhang, Gao Jing, Yin Jiajing, Gu Liping, Liu Xing, Chen Su, Huang Qianfang, Lu Huifang, Yang Yuemin, Zhou Hu, Wang Yufan, Peng Yongde

机构信息

Department of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zuchongzhi Road, Shanghai 201203, China.

出版信息

J Proteome Res. 2016 Feb 5;15(2):628-37. doi: 10.1021/acs.jproteome.5b01030. Epub 2016 Jan 27.

Abstract

Gestational diabetes mellitus (GDM) is considered as an early stage of type 2 diabetes mellitus. In this study, we compared demographic and clinical data between six GDM subjects and six normal glucose tolerance (NGT; healthy controls) subjects and found that homeostasis model of assessment for insulin resistance index (HOMA-IR) increased in GDM. Many previous studies demonstrated that omental adipose tissue dysfunction could induce insulin resistance. Thus, to investigate the cause of insulin resistance in GDM, we used label-free proteomics to identify differentially expressed proteins in omental adipose tissues from GDM and NGT subjects (data are available via ProteomeXchange with identifier PXD003095). A total of 3528 proteins were identified, including 66 significantly changed proteins. Adipocyte plasma membrane-associated protein (APMAP, a.k.a. C20orf3), one of the differentially expressed proteins, was down-regulated in GDM omental adipose tissues. Furthermore, mature 3T3-L1 adipocytes were used to simulate omental adipocytes. The inhibition of APMAP expression by RNAi impaired insulin signaling and activated NFκB signaling in these adipocytes. Our study revealed that the down-regulation of APMAP in omental adipose tissue may play an important role in insulin resistance in the pathophysiology of GDM.

摘要

妊娠期糖尿病(GDM)被认为是2型糖尿病的早期阶段。在本研究中,我们比较了6名GDM受试者和6名糖耐量正常(NGT;健康对照)受试者的人口统计学和临床数据,发现GDM患者的胰岛素抵抗指数稳态模型评估(HOMA-IR)升高。许多先前的研究表明,网膜脂肪组织功能障碍可诱导胰岛素抵抗。因此,为了研究GDM中胰岛素抵抗的原因,我们使用无标记蛋白质组学来鉴定GDM和NGT受试者网膜脂肪组织中差异表达的蛋白质(数据可通过ProteomeXchange获得,标识符为PXD003095)。共鉴定出3528种蛋白质,其中66种蛋白质有显著变化。差异表达的蛋白质之一脂肪细胞质膜相关蛋白(APMAP,又名C20orf3)在GDM网膜脂肪组织中表达下调。此外,使用成熟的3T3-L1脂肪细胞模拟网膜脂肪细胞。RNAi抑制APMAP表达会损害这些脂肪细胞中的胰岛素信号传导并激活NFκB信号传导。我们的研究表明,网膜脂肪组织中APMAP的下调可能在GDM病理生理学中的胰岛素抵抗中起重要作用。

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