Insulin signaling pathways in muscle tissue play a major role in maintaining glucose homeostasis. Dysregulation in these pathways results in the onset of serious metabolic disorders like type 2 diabetes. Robustness is an essential characteristic of insulin signaling pathways that ensures reliable signal transduction in the presence of perturbations as a result of several feedback mechanisms. Integral control, according to control engineering, provides reliable setpoint tracking and disturbance rejection. The presence of negative feedback and integrating process is crucial for biological processes to achieve integral control. The existence of an integral controller leads to the rejection of perturbations which resulted in the robust regulation of biochemical entities within acceptable levels. In the present in silico research work, the presence of integral control in the protein kinase C ζ - insulin receptor substrate-1 (PKC ζ-IRS1) pathway is identified, verified mathematically and model is simulated in Cell Designer. The data is exported to Minitab software and robustness analysis is carried out statistically using the Mann-Whitney test. The p-value of the results obtained with given parameters perturbed by 1% is greater than the significance level of 0.05 (0.2132 for 1% error in k7(rate constant of IRS1 phosphorylation), 0.2096 for −1% error in k7, 0.9037 for both 1% error in insulin and 0.9037 for 1% error in k1(association rate constant of the first molecule of insulin to bind the insulin receptor), indicated that our hypothesis is proved The results satisfactorily indicate that even when perturbations are present, glucose homeostasis in muscle tissue is robust due to the presence of integral regulation in the PKC ζ-IRS1 insulin signaling pathways. In this paper, we have analysed the findings from the framework of robust control theory, which has allowed us to examine that how PKC ζ-IRS1 insulin signaling pathways produces desired output in presence of perturbations.

肌肉组织中的胰岛素信号通路在维持葡萄糖稳态中起主要作用。这些通路的失调会导致严重的代谢紊乱，如 2 型糖尿病。稳健性是胰岛素信号通路的基本特征，可确保在存在扰动的情况下可靠的信号转导，这是由于几种反馈机制的结果。根据控制工程，积分控制提供可靠的设定点跟踪和干扰抑制。负反馈和积分过程的存在对于生物过程实现积分控制至关重要。积分控制器的存在导致抑制扰动，从而导致生化实体在可接受水平内的稳健调节。目前在 silico研究工作，蛋白激酶 C ζ - 胰岛素受体底物 1 (PKC ζ ) 中存在积分控制-IRS1) 通路在 Cell Designer 中进行识别、数学验证和模型模拟。将数据导出到 Minitab 软件，并使用 Mann-Whitney 检验统计执行稳健性分析。在给定参数扰动 1% 的情况下获得的结果的 p 值大于显着性水平 0.05（k7 中 1% 误差为 0.2132（IRS1 磷酸化速率常数），k7 中为 -1% 误差为 0.2096，k7 中为 0.9037胰岛素的 1% 误差和 k1（第一个胰岛素分子与胰岛素受体结合的结合速率常数）的 1% 误差为 0.9037，表明我们的假设得到了证明。结果令人满意地表明，即使存在扰动，葡萄糖稳态由于 PKC ζ中存在整体调节，因此肌肉组织中的细胞是稳健的-IRS1 胰岛素信号通路。在本文中，我们分析了稳健控制理论框架的发现，这使我们能够检查 PKC ζ -IRS1 胰岛素信号通路如何在存在扰动的情况下产生所需的输出。