Kuznetsova T N, Ignat'eva E V, Mordvinov V A, Katokhin A V, Shamanina M Iu, Oshchepkov D Iu, Kolchanov N A
Usp Fiziol Nauk. 2008 Jan-Mar;39(1):3-22.
Insulin is the important regulator of adipose cell metabolism and activates the branched out network of the signaling pathways supervising glucose transport, glycogen synthesis, lipogenesis stimulation, lipolysis inhibition and adipokine secretion. The purpose of our work is the analysis of structure of regulatory contours providing the response of mammalian adipocytes to insulin. With use of computer technology GeneNet adipocyte regulatory-effector network has been reconstructed. The network generalizes experimental data concerning the main insulin-dependent signaling pathways and their targets in a context insulin-sensitive metabolic processes and transcription events. Analysis of the network revealed positive and negative regulatory contours including MAP kinase-, Cbl/TC10- and P13K-dependent signaling pathways. Regulatory contours functioning with participation of transcription factors SREBP-1c, PPARgamma/RXRalpha, C/EBPalpha, FOXO1 are defined also. The major effectors of regulatory contours are glucose carrier GLUT4, and kinase mTOR.
胰岛素是脂肪细胞代谢的重要调节因子，可激活监督葡萄糖转运、糖原合成、脂肪生成刺激、脂解抑制和脂肪因子分泌的信号通路分支网络。我们工作的目的是分析调控轮廓的结构，这些调控轮廓使哺乳动物脂肪细胞对胰岛素产生反应。利用计算机技术重建了基因网络脂肪细胞调节效应器网络。该网络概括了关于主要胰岛素依赖性信号通路及其在胰岛素敏感代谢过程和转录事件中的靶点的实验数据。对该网络的分析揭示了包括丝裂原活化蛋白激酶（MAP激酶）、Cbl/TC10和磷脂酰肌醇-3激酶（PI3K）依赖性信号通路在内的正负调控轮廓。还确定了在转录因子固醇调节元件结合蛋白-1c（SREBP-1c）、过氧化物酶体增殖物激活受体γ/维甲酸X受体α（PPARγ/RXRα）、CCAAT增强子结合蛋白α（C/EBPα）、叉头框蛋白O1（FOXO1）参与下起作用的调控轮廓。调控轮廓的主要效应器是葡萄糖载体GLUT4和激酶雷帕霉素靶蛋白（mTOR）。
