Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity.
Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity.
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DOI：
10.1038/msb.2008.50
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发表时间：
2008
影响因子：
9.9
通讯作者：
Mootha, Vamsi K.
中科院分区：
文献类型：
--
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.
一夜禁食后的葡萄糖摄入会触发胰岛素依赖的体内平衡程序，在糖尿病中发生改变。与这一转变相关的全部生化变化目前尚不清楚。我们开发了一种基于质谱的策略，可以同时测量葡萄糖摄入后的191种代谢物。在两组健康个体（n=22和25）中，18种血浆代谢物发生了可重复的变化，包括胆汁酸、尿素循环中间体和嘌呤降解产物，这些物质以前都与葡萄糖稳态无关。代谢动力学还揭示了胰岛素在四个关键轴上的已知作用——蛋白质分解、脂肪分解、生酮和糖酵解——反映了从分解代谢到合成代谢的转变。在糖尿病前期患者（n=25）中，我们观察到与胰岛素抵抗相关的所有四个轴的反应都变钝。多变量分析显示甘油和亮氨酸/异亮氨酸（分别是脂肪分解和蛋白质分解的标志）的下降共同提供了胰岛素敏感性的最强预测因子。这一观察结果表明，有些人有选择性地抵抗胰岛素对蛋白质分解的抑制，而另一些人则有选择性地抵抗胰岛素对脂肪分解的抑制。我们的发现为使用代谢谱来定义个体的“胰岛素反应谱”奠定了基础，这在预测糖尿病及其并发症和指导治疗方面可能具有价值。
Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy.
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影响因子：
15.9
作者：
MATEOS, FA;PUIG, JG;FOX, IH
通讯作者：
FOX, IH
影响因子：
64.8
作者：
Watanabe, M;Houten, SM;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
4.8
作者：
Yamaoka, T;Kondo, M;Itakura, M
通讯作者：
Itakura, M
影响因子：
15.9
作者：
ANGELIN, B;BJORKHEM, I;EWERTH, S
通讯作者：
EWERTH, S
DOI：
10.1152/ajpendo.1996.270.2.e273
发表时间：
1996-02-01
影响因子：
5.1
作者：
Luzi, L;Castellino, P;DeFronzo, RA
通讯作者：
DeFronzo, RA