Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics.
Compensatory Islet Response to Insulin Resistance Revealed by Quantitative Proteomics.
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DOI：
10.1021/acs.jproteome.5b00587
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发表时间：
2015-08-07
影响因子：
4.4
通讯作者：
Kulkarni RN
中科院分区：
文献类型：
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作者：
El Ouaamari A;Zhou JY;Liew CW;Shirakawa J;Dirice E;Gedeon N;Kahraman S;De Jesus DF;Bhatt S;Kim JS;Clauss TR;Camp DG 2nd;Smith RD;Qian WJ;Kulkarni RN
代偿性胰岛反应是人类和啮齿类动物糖尿病前期胰岛素抵抗状态的一个明显特征。为了确定表征适应性反应的胰岛蛋白质组的改变，我们通过LC-MS（/MS）分析了5个月大的雄性对照组、高脂肪饮食喂养（HFD）或肥胖的ob/ob小鼠的胰岛，并量化了约1,100个胰岛蛋白（至少两种肽），错误发现率<1%。在两组之间，约有350种蛋白质的丰度发生了显著变化。大多数改变对两种模型都是共同的，并且分别使用选择的反应监测和Western blots通过靶向定量验证了约40个蛋白质和12个蛋白质的变化。两组胰岛素抵抗的胰岛均表现出控制能量代谢、氧化磷酸化、激素加工和分泌途径的蛋白质表达减少。相反，参与蛋白质合成和折叠的分子表达增加表明，在两种胰岛素抵抗模型中，内质网应激反应、细胞存活和增殖都有影响。总之，我们报告了一个独特的比较胰岛蛋白质组，重点是代偿反应在两种胰岛素抵抗的啮齿动物模型，不是明显的糖尿病。这些数据为科学界开展旨在增强糖尿病患者β细胞质量的进一步研究提供了宝贵的候选蛋白资源。数据可通过MassIVE存储库获得，其登录号为MSV000079093。
Compensatory islet response is a distinct feature of the pre-diabetic insulin resistant state in humans and rodents. To identify alterations in the islet proteome that characterize the adaptive response, we analyzed islets from five-month-old male control, high-fat diet fed (HFD) or obese ob/ob mice by LC-MS(/MS) and quantified ~1,100 islet proteins (at least two peptides) with a false discovery rate <1%. Significant alterations in abundance were observed for ~350 proteins between groups. A majority of alterations were common to both models, and the changes of a subset of ~40 proteins and 12 proteins were verified by targeted quantification using selected reaction monitoring and Western blots, respectively. The insulin resistant islets in both groups exhibited reduced expression of proteins controlling energy metabolism, oxidative phosphorylation, hormone processing, and secretory pathways. Conversely, an increased expression of molecules involved in protein synthesis and folding suggested effects in endoplasmic reticulum stress response, cell survival, and proliferation in both insulin resistant models. In summary, we report a unique comparison of the islet proteome that is focused on the compensatory response in two insulin resistant rodent models that are not overtly diabetic. These data provide a valuable resource of candidate proteins to the scientific community to undertake further studies aimed at enhancing β-cell mass in patients with diabetes. The data are available via the MassIVE repository, with accession MSV000079093.