Proteomic analysis of serum biomarkers for prediabetes using the Long-Evans Agouti rat, a spontaneous animal model of type 2 diabetes mellitus.
Proteomic analysis of serum biomarkers for prediabetes using the Long-Evans Agouti rat, a spontaneous animal model of type 2 diabetes mellitus.
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DOI：
10.1111/jdi.12638
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发表时间：
2017-09
影响因子：
3.2
通讯作者：
Kaburagi Y
中科院分区：
文献类型：
--
作者：
Takahashi E;Unoki-Kubota H;Shimizu Y;Okamura T;Iwata W;Kajio H;Yamamoto-Honda R;Shiga T;Yamashita S;Tobe K;Okumura A;Matsumoto M;Yasuda K;Noda M;Kaburagi Y
为了确定与2型糖尿病进展相关的候选血清分子，对自发性2型糖尿病动物模型Long - Evans Agouti （LEA）大鼠进行了差异血清蛋白质组学分析。我们使用8周龄和16周龄LEA和对照褐挪威（BN）大鼠（n = 4/组）的血清样本进行了定量蛋白质组学分析。采用8 -、16 -和24周龄LEA （n = 4/每组）和BN大鼠（n = 5/每组）收集的血清，通过多重反应监测分析验证差异表达蛋白。在验证的蛋白中，我们还研究了丝氨酸蛋白酶抑制剂A3 （SERPINA3）的人类同源物与2型糖尿病的可能相关性。利用2 - D荧光差异凝胶电泳分析和随后的液相色谱多重反应监测分析显示，在所有三个时间点，LEA大鼠和BN大鼠的血清中五种蛋白质的水平都发生了差异。其中，与年龄匹配的BN大鼠相比，LEA大鼠血清中的SERPINA3N明显升高。2型糖尿病患者血清SERPINA3水平也明显高于健康对照组。此外，糖化血红蛋白、空腹胰岛素和估计的肾小球滤过率与SERPINA3水平独立相关。这些发现表明SERPINA3可能在2型糖尿病早期的发展中起作用，尽管需要进一步的复制研究和功能调查。
To identify candidate serum molecules associated with the progression of type 2 diabetes mellitus, differential serum proteomic analysis was carried out on a spontaneous animal model of type 2 diabetes mellitus without obesity, the Long‐Evans Agouti (LEA) rat. We carried out quantitative proteomic analysis using serum samples from 8‐ and 16‐week‐old LEA and control Brown Norway (BN) rats (n = 4/group). Differentially expressed proteins were validated by multiple reaction monitoring analysis using the sera collected from 8‐, 16‐, and 24‐week‐old LEA (n = 4/each group) and BN rats (n = 5/each group). Among the validated proteins, we also examined the possible relevance of the human homolog of serine protease inhibitor A3 (SERPINA3) to type 2 diabetes mellitus. The use of 2‐D fluorescence difference gel electrophoresis analysis and the following liquid chromatography‐multiple reaction monitoring analysis showed that the serum levels of five proteins were differentially changed between LEA rats and BN rats at all three time‐points examined. Among the five proteins, SERPINA3N was increased significantly in the sera of LEA rats compared with age‐matched BN rats. The serum level of SERPINA3 was also found to be significantly higher in type 2 diabetes mellitus patients than in healthy control participants. Furthermore, glycated hemoglobin, fasting insulin and estimated glomerular filtration rate were independently associated with the SERPINA3 levels. These findings suggest a possible role for SERPINA3 in the development of the early stages of type 2 diabetes mellitus, although further replication studies and functional investigations regarding their role are required.
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DOI：
10.1074/mcp.m113.034769
发表时间：
2014-01
期刊：
Molecular & cellular proteomics : MCP
影响因子：
--
作者：
Hebert AS;Richards AL;Bailey DJ;Ulbrich A;Coughlin EE;Westphall MS;Coon JJ
通讯作者：
Coon JJ
影响因子：
7.7
作者：
Zhang B;Zhou KK;Ma JX
通讯作者：
Ma JX
影响因子：
5.1
作者：
Yuan, Guoyue;Zhou, Libin;Chen, Mingdao
通讯作者：
Chen, Mingdao
影响因子：
2.3
作者：
El Mesallamy, Hala O.;Hamdy, Nadia M.;Amin, Ashraf I.
通讯作者：
Amin, Ashraf I.
影响因子：
168.9
作者：
Kahn, Steven E.;Cooper, Mark E.;Del Prato, Stefano
通讯作者：
Del Prato, Stefano