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采用蛋白质组学方法鉴定与韩国腹型肥胖糖尿病患者疾病进展相关的血清生物标志物。

Proteomics approach to identify serum biomarkers associated with the progression of diabetes in Korean patients with abdominal obesity.

机构信息

Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung-si, Gangwon-do, South Korea.

Catholic Kwandong University, International St. Mary's Hospital, Incheon Metropolitan City, South Korea.

出版信息

PLoS One. 2019 Sep 10;14(9):e0222032. doi: 10.1371/journal.pone.0222032. eCollection 2019.

Abstract

Type 2 diabetes is a metabolic disease with a group of metabolic derangements and inflammatory reactants in the serum. Despite the substantial public health implications, markers of diabetes progression with abdominal obesity are still needed to facilitate early detection and treatment. In this study, we performed a proteomic approach to identify differential target proteins underlying diabetes progression in patients with abdominal obesity. Proteomic differences were investigated in the serum of controls and patients with prediabetes or diabetes with or without abdominal obesity by 2-DE combined with MALDI-TOF-MS. Proteomics data were validated by western blot analyses and major protein-protein interactions were assessed using a network analysis with String database. Among 245 matched protein spots, 36 exhibited marked differences in normal patients with abdominal obesity, prediabetes, and diabetes compared to levels in normal patients without abdominal obesity. Seven (Alpha-1-antichymotrypsin, Alpha-1-antitrypsin, Apolipoprotein A-I, haptoglobin, retinol-binding protein 4, transthyretin, and zinc-alpha2-glycoprotein) of these spots exhibited significant differences between normal and prediabetes/diabetes patients. After a network analysis, functional annotation using Gene Ontology indicated that most of the identified proteins were involved in lipid transport, lipid localization, and the regulation of serum lipoprotein particle levels. Our results indicated that variation in the levels of these identified protein biomarkers has been reported in normal, prediabetes and diabetic Assessment of the levels of these biomarkers may contribute to the development of biomarkers for not only early diagnosis but also in prognosis of diabetes mellitus type 2.

摘要

2 型糖尿病是一种代谢性疾病,其血清中存在一组代谢紊乱和炎症反应物。尽管对公共健康有重大影响,但仍需要与腹部肥胖相关的糖尿病进展标志物来促进早期发现和治疗。在这项研究中,我们采用蛋白质组学方法来鉴定腹部肥胖的糖尿病患者中潜在的糖尿病进展的差异靶蛋白。通过 2-DE 结合 MALDI-TOF-MS 分析了对照组和患有前驱糖尿病或糖尿病的患者(伴或不伴腹部肥胖)的血清中的蛋白质组差异。通过 Western blot 分析验证蛋白质组学数据,并使用带有 String 数据库的网络分析评估主要的蛋白质-蛋白质相互作用。在 245 个匹配的蛋白质斑点中,有 36 个在正常伴有腹部肥胖、前驱糖尿病和糖尿病的患者中与正常无腹部肥胖的患者相比表现出明显差异。其中 7 个(Alpha-1-抗糜蛋白酶、Alpha-1-抗胰蛋白酶、载脂蛋白 A-I、触珠蛋白、视黄醇结合蛋白 4、转甲状腺素蛋白和锌-α2-糖蛋白)在正常和前驱糖尿病/糖尿病患者之间表现出显著差异。经过网络分析,使用 Gene Ontology 进行功能注释表明,大多数鉴定出的蛋白质参与脂质转运、脂质定位和血清脂蛋白颗粒水平的调节。我们的结果表明,这些已鉴定的蛋白质生物标志物的水平变化在正常、前驱糖尿病和糖尿病患者中均有报道。评估这些生物标志物的水平可能有助于不仅早期诊断而且 2 型糖尿病预后的生物标志物的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96c8/6736247/881ab5c75733/pone.0222032.g001.jpg

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