Metabolite profiles during oral glucose challenge.
Metabolite profiles during oral glucose challenge.
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作者：
Ho JE;Larson MG;Vasan RS;Ghorbani A;Cheng S;Rhee EP;Florez JC;Clish CB;Gerszten RE;Wang TJ
为了确定葡萄糖代谢的不同生物学途径，我们对社区人群口服葡萄糖耐量试验（OGTT）后的生化变化进行了系统评估。在OGTT前后对377名非糖尿病Framingham Offspring队列参与者（平均年龄57岁，42%为女性，BMI为30 kg/m2）进行代谢谱分析。使用配对学生t检验、聚类分析和多变量线性回归来评估代谢物水平的变化，以检查与胰岛素抵抗相关的差异。在所检测的110种代谢物中，有91种随OGTT变化显著（P≤0.0005）。OGTT后氨基酸、β-羟基丁酸和三羧酸循环中间体减少，糖酵解产物增加，与生理性胰岛素作用一致。OGTT影响的其他途径包括血清素衍生物、尿素循环代谢物和B族维生素的减少。我们还观察到共轭胆汁酸的增加和非共轭胆汁酸的减少。胰岛素抵抗患者β-羟基丁酸、异亮氨酸、乳酸和吡哆酸的变化减弱。我们的研究结果证实了91种代谢物的变化，这些代谢物代表了不同的生物学途径，这些途径在OGTT的反应中受到干扰。我们还鉴定了代谢物反应，以区分有和没有胰岛素抵抗的个体。这些发现表明，在糖尿病前期，OGTT可以揭示独特的代谢表型。
To identify distinct biological pathways of glucose metabolism, we conducted a systematic evaluation of biochemical changes after an oral glucose tolerance test (OGTT) in a community-based population. Metabolic profiling was performed on 377 nondiabetic Framingham Offspring cohort participants (mean age 57 years, 42% women, BMI 30 kg/m2) before and after OGTT. Changes in metabolite levels were evaluated with paired Student t tests, cluster-based analyses, and multivariable linear regression to examine differences associated with insulin resistance. Of 110 metabolites tested, 91 significantly changed with OGTT (P ≤ 0.0005 for all). Amino acids, β-hydroxybutyrate, and tricarboxylic acid cycle intermediates decreased after OGTT, and glycolysis products increased, consistent with physiological insulin actions. Other pathways affected by OGTT included decreases in serotonin derivatives, urea cycle metabolites, and B vitamins. We also observed an increase in conjugated, and a decrease in unconjugated, bile acids. Changes in β-hydroxybutyrate, isoleucine, lactate, and pyridoxate were blunted in those with insulin resistance. Our findings demonstrate changes in 91 metabolites representing distinct biological pathways that are perturbed in response to an OGTT. We also identify metabolite responses that distinguish individuals with and without insulin resistance. These findings suggest that unique metabolic phenotypes can be unmasked by OGTT in the prediabetic state.
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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.
通讯作者：
Mootha, Vamsi K.
影响因子：
168.9
作者：
Tabak, Adam G.;Jokela, Markus;Akbaraly, Tasnime N.;Brunner, Eric J.;Kivimaki, Mika;Witte, Daniel R.
通讯作者：
Witte, Daniel R.
影响因子：
--
作者：
Lin, Shuhai;Yang, Zhu;Cai, Zongwei
通讯作者：
Cai, Zongwei
影响因子：
3.2
作者：
LECHIN, F;VANDERDIJS, B;JIMENEZ, V
通讯作者：
JIMENEZ, V
影响因子：
3.7
作者：
Suhre K;Meisinger C;Döring A;Altmaier E;Belcredi P;Gieger C;Chang D;Milburn MV;Gall WE;Weinberger KM;Mewes HW;Hrabé de Angelis M;Wichmann HE;Kronenberg F;Adamski J;Illig T
通讯作者：
Illig T