Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.

Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks.
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基于差异表达网络的2型糖尿病时空分析

DOI:
10.1038/srep02268
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Chen, Luonan
Chen, Luonan
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sun, Shao-Yan;Liu, Zhi-Ping;Zeng, Tao;Wang, Yong;Chen, Luonan

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T2DM是一个复杂的动态依赖于多种组织、疾病状态和因素的相互作用。然而,大多数现有的工作致力于从一个静态组织,个体因素或单一状态来表征其病理生理。在这里,我们通过开发一种新的分子网络形式,即“差异表达网络”(DEN),对T2DM进行时空分析,该网络可以反映网络水平上的表型差异。静态den显示,三种组织(白色脂肪、骨骼肌和肝脏)均存在严重的炎症和代谢紊乱,其中肝脏代谢功能受到严重影响。动态分析显示脂肪和肝脏代谢功能的改变与胰岛素抵抗(IR)恶化一致。对IR通路的深入研究确定了“疾病相互作用”,揭示了脂肪和肌肉中IR恶化比SlC2A4更早。我们的分析也提供了胰岛素分泌增加是糖尿病IR的根本原因的证据。
T2DM is complex in its dynamical dependence on multiple tissues, disease states and factors' interactions. However, most existing work devoted to characterizing its pathophysiology from one static tissue, individual factors, or single state. Here we perform a spatio-temporal analysis on T2DM by developing a new form of molecular network, i.e. ‘differential expression network’ (DEN), which can reflect phenotype differences at network level. Static DENs show that three tissues (white adipose, skeletal muscle and liver) all suffer from severe inflammation and perturbed metabolism, among which metabolic functions are seriously affected in liver. Dynamical analysis on DENs reveals metabolic function changes in adipose and liver are consistent with insulin resistance (IR) deterioration. Close investigation on IR pathway identifies ‘disease interactions’, revealing that IR deterioration is earlier than that on SlC2A4 in adipose and muscle. Our analysis also provides evidence that rising of insulin secretion is the root cause of IR in diabetes.
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