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金属蛋白与载脂蛋白C:通过比较蛋白质组学和脂质组学在ZDF大鼠中筛选出的2型糖尿病候选血浆生物标志物。

Metalloproteins and apolipoprotein C: candidate plasma biomarkers of T2DM screened by comparative proteomics and lipidomics in ZDF rats.

作者信息

Wang Shuai, Lu Zhiyuan, Wang Yuxin, Zhang Tianran, He Xiaodong

机构信息

Institute of Toxicology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250012 Shandong China.

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, 250012 Shandong China.

出版信息

Nutr Metab (Lond). 2020 Aug 12;17:66. doi: 10.1186/s12986-020-00488-2. eCollection 2020.

Abstract

BACKGROUND

Early diagnosis of type 2 diabetes mellitus (T2DM) is still difficult. Screening of plasma biomarkers has great significance of optimizing diagnosis and predicting the complications of T2DM.

METHODS

We used a special diet, Purina #5008, to induce diabetes in Zucker leptin receptor gene-deficient rats (fa/fa) to establish Zucker diabetic fatty (ZDF) rats, simulating the early stage of T2DM. The differentially expressed proteins (DEP) and lipids (DEL), as potential biomarkers, were screened to compare the plasma expression levels in ZDF rats and their basic diet-fed wild-type controls (fa/+) by Tandem Mass Tags (TMT) and liquid chromatography-tandem mass spectrometry.

RESULTS

These two groups had different plasma proteins and lipids profiles consisting of 84 DEPs and, 179 DELs identified in the positive ion mode and 178 DELs in the negative ion mode, respectively. Enrichment analysis of these different indicators showed that oxidative stress, insulin resistance and metabolic disorders of glycan and lipid played an important role in generating the difference. Some markers can be used as candidate biomarkers in prediction and treatments of T2DM, such as ceruloplasmin, apolipoprotein C-I, apolipoprotein C-II and apolipoprotein C-IV.

CONCLUSION

These plasma differences help to optimize the diagnosis and predict the complications of T2DM, although this remains to be verified in the crowd. Trace elements related-metalloproteins, such as ceruloplasmin, and lipid metabolism and transport-related apolipoprotein C are expected to be candidate biomarkers of T2DM and should be given more attention.

摘要

背景

2型糖尿病(T2DM)的早期诊断仍然困难。血浆生物标志物的筛查对于优化T2DM的诊断和预测并发症具有重要意义。

方法

我们使用特殊饮食普瑞纳#5008诱导Zucker瘦素受体基因缺陷大鼠(fa/fa)患糖尿病,以建立Zucker糖尿病脂肪大鼠(ZDF),模拟T2DM的早期阶段。通过串联质谱标签(TMT)和液相色谱-串联质谱法筛选差异表达蛋白(DEP)和脂质(DEL)作为潜在生物标志物,比较ZDF大鼠及其基础饮食喂养的野生型对照(fa/+)的血浆表达水平。

结果

这两组的血浆蛋白质和脂质谱不同,分别在正离子模式下鉴定出84种DEP和179种DEL,在负离子模式下鉴定出178种DEL。对这些不同指标的富集分析表明,氧化应激、胰岛素抵抗以及聚糖和脂质的代谢紊乱在产生差异中起重要作用。一些标志物可作为T2DM预测和治疗的候选生物标志物,如铜蓝蛋白、载脂蛋白C-I、载脂蛋白C-II和载脂蛋白C-IV。

结论

这些血浆差异有助于优化T2DM的诊断和预测并发症,尽管这仍有待在人群中得到验证。与微量元素相关的金属蛋白,如铜蓝蛋白,以及与脂质代谢和转运相关的载脂蛋白C有望成为T2DM的候选生物标志物,应给予更多关注。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1db/7425165/d4624843c108/12986_2020_488_Fig1_HTML.jpg

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