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

机译:网膜脂肪组织的蛋白质组学分析鉴定妊娠糖尿病中脂肪细胞血浆膜相关蛋白(APMAP)的新功能。

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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 NF kappa B 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.
机译:妊娠期糖尿病(GDM)被认为是2型糖尿病的早期阶段。在这项研究中,我们比较了6名GDM受试者和6名正常糖耐量(NGT;健康对照)受试者的人口统计学和临床​​数据,发现GDM中胰岛素抵抗指数(HOMA-IR)评估的稳态模型增加。先前的许多研究表明,网膜脂肪组织功能障碍可诱发胰岛素抵抗。因此,为了研究GDM中胰岛素抵抗的原因,我们使用了无标记蛋白质组学来鉴定GDM和NGT受试者的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)。总共鉴定出3528种蛋白质,包括66种显着变化的蛋白质。脂肪细胞质膜相关蛋白(APMAP,a.k.a. C20orf3)(一种差异表达的蛋白)在GDM网膜脂肪组织中被下调。此外,成熟的3T3-L1脂肪细胞被用来模拟网膜脂肪细胞。 RNAi对APMAP表达的抑制作用削弱了这些脂肪细胞中的胰岛素信号传导并激活了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的病理生理中对胰岛素抵抗具有重要作用。

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