Drexel University, Department of Physics, Philadelphia, PA 19104-2875, USA.
IET Syst Biol. 2010 Jan;4(1):64-81. doi: 10.1049/iet-syb.2008.0178.
The authors have applied the dynamic sensitivity and control analyses to study the GLUT4 metabolic insulin signalling pathways, based on the models developed by Sedaghat et al. They have calculated the time-dependent sensitivities of the concentration of the membrane GLUT4 with respect to all reaction parameters (reaction rate constants and initial concentrations of the effectors). These time-dependent sensitivities provide dynamic information about pathways, in particular, the separate roles of the negative and positive feedbacks in the network. In addition, the integrated sensitivities of the membrane GLUT4 have been used to rank the potential drug targets according to the accumulated influence of each reaction rate or initial concentration on the membrane GLUT4. The results are consistent with experimental facts and predictions of drug targets in the literature. Furthermore, a strategy is developed using dynamic sensitivities to control the accumulated amount of membrane GLUT4 over a period of time for a fixed amount of insulin input. This strategy is then applied to rank possible mechanisms of insulin resistance. The results are also in agreement with those suggested in the literature.
作者应用动态灵敏度和控制分析研究 GLUT4 代谢胰岛素信号通路，基于 Sedaghat 等人开发的模型。他们计算了膜 GLUT4 浓度对所有反应参数（反应速率常数和效应物的初始浓度）的时变灵敏度。这些时变灵敏度提供了有关途径的动态信息，特别是网络中负反馈和正反馈的单独作用。此外，还使用整合灵敏度根据每个反应速率或初始浓度对膜 GLUT4 的累积影响对潜在药物靶点进行排序。结果与实验事实和文献中药物靶点的预测一致。此外，还使用动态灵敏度开发了一种策略，以在固定胰岛素输入量的情况下控制一段时间内膜 GLUT4 的累积量。然后，该策略用于对胰岛素抵抗的可能机制进行排序。结果也与文献中提出的结果一致。
