Insulin sensitivity is reflected by characteristic metabolic fingerprints--a Fourier transform mass spectrometric non-targeted metabolomics approach.
Insulin sensitivity is reflected by characteristic metabolic fingerprints--a Fourier transform mass spectrometric non-targeted metabolomics approach.
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DOI：
10.1371/journal.pone.0013317
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发表时间：
2010-10-15
期刊：
影响因子：
3.7
通讯作者：
Lehmann R
中科院分区：
文献类型：
--
作者：
Lucio M;Fekete A;Weigert C;Wägele B;Zhao X;Chen J;Fritsche A;Häring HU;Schleicher ED;Xu G;Schmitt-Kopplin P;Lehmann R
表面健康的个体体内胰岛素敏感性下降表明患 2 型糖尿病的风险很高。根据Matsuda等人的公式研究不同全身胰岛素敏感性个体的代谢指纹。 (ISIMatsuda) 通过非靶向代谢组学方法，我们的目标是 a) 找出可疑且改变的代谢模式，b) 根据 ISI 估计与这些变化相关的阈值，以及 c) 识别负责区分两种模式的代谢途径。通过应用输注离子回旋共振傅里叶变换质谱法，我们分析了 46 名表现出高至低胰岛素敏感性的非糖尿病受试者的血浆。正交偏最小二乘模型揭示了一个由 28 名个体组成的群体，其代谢指纹的改变与胰岛素敏感性下降相关。该组可从 18 名具有可疑代谢模式的受试者中分离出来。正交信号校正得分散点图建议区分这两组的 ISIMatsuda 阈值为 15。值得注意的是，在不同的模型中确定了一个由 8 个人代表的潜在亚组（ISIMatsuda 值在 8.5 到 15 之间）。该亚组可能表明代谢过渡状态，因为它已经位于胰岛素敏感性下降的个体群内，但代谢指纹仍然显示出与未受影响个体的一些相似性（ISI > 15）。此外，根据使用代谢注释界面的数据评估，在脂质代谢途径（花生四烯酸代谢、必需脂肪酸代谢和不饱和脂肪酸生物合成）、类固醇激素生物合成和胆汁酸代谢中检测到了可疑和改变的代谢指纹之间代谢物强度差异最多的数量 MassTRIX。我们的结果表明，反映胰岛素敏感性变化的代谢模式改变（ISIMatsuda）主要由脂质相关途径主导。此外，异质代谢物指纹反映的代谢过渡状态可能先于代谢的严重改变。我们的研究结果为糖尿病前期发病机制的新见解提供了前景。
A decline in body insulin sensitivity in apparently healthy individuals indicates a high risk to develop type 2 diabetes. Investigating the metabolic fingerprints of individuals with different whole body insulin sensitivity according to the formula of Matsuda, et al. (ISIMatsuda) by a non-targeted metabolomics approach we aimed a) to figure out an unsuspicious and altered metabolic pattern, b) to estimate a threshold related to these changes based on the ISI, and c) to identify the metabolic pathways responsible for the discrimination of the two patterns. By applying infusion ion cyclotron resonance Fourier transform mass spectrometry, we analyzed plasma of 46 non-diabetic subjects exhibiting high to low insulin sensitivities. The orthogonal partial least square model revealed a cluster of 28 individuals with alterations in their metabolic fingerprints associated with a decline in insulin sensitivity. This group could be separated from 18 subjects with an unsuspicious metabolite pattern. The orthogonal signal correction score scatter plot suggests a threshold of an ISIMatsuda of 15 for the discrimination of these two groups. Of note, a potential subgroup represented by eight individuals (ISIMatsuda value between 8.5 and 15) was identified in different models. This subgroup may indicate a metabolic transition state, since it is already located within the cluster of individuals with declined insulin sensitivity but the metabolic fingerprints still show some similarities with unaffected individuals (ISI >15). Moreover, the highest number of metabolite intensity differences between unsuspicious and altered metabolic fingerprints was detected in lipid metabolic pathways (arachidonic acid metabolism, metabolism of essential fatty acids and biosynthesis of unsaturated fatty acids), steroid hormone biosyntheses and bile acid metabolism, based on data evaluation using the metabolic annotation interface MassTRIX. Our results suggest that altered metabolite patterns that reflect changes in insulin sensitivity respectively the ISIMatsuda are dominated by lipid-related pathways. Furthermore, a metabolic transition state reflected by heterogeneous metabolite fingerprints may precede severe alterations of metabolism. Our findings offer future prospects for novel insights in the pathogenesis of the pre-diabetic phase.
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影响因子：
9.9
作者：
Shaham, Oded;Wei, Ru;Wang, Thomas J.;Ricciardi, Catherine;Lewis, Gregory D.;Vasan, Ramachandran S.;Carr, Steven A.;Thadhani, Ravi;Gerszten, Robert E.;Mootha, Vamsi K.
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通讯作者：
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