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首页> 外文期刊>Journal of Theoretical Biology >Insulin receptor binding kinetics: Modeling and simulation studies
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Insulin receptor binding kinetics: Modeling and simulation studies

机译：胰岛素受体结合动力学：建模和模拟研究

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摘要

Biological actions of insulin regulate glucose metabolism and other essential physiological functions. Binding of insulin to its cell surface receptor initiates signal transduction pathways that mediate cellular responses. Thus, it is of great interest to understand the mechanisms underlying insulin receptor binding kinetics. Interestingly, negative cooperative interactions are observed at high insulin concentrations while positive cooperativity may be present at low insulin concentrations. Clearly, insulin receptor binding kinetics cannot be simply explained by a classical bimolecular reaction. Mature insulin receptors have a dimeric structure capable of binding two molecules of insulin. The binding affinity of the receptor for the second insulin molecule is significantly lower than for the first bound insulin molecule. In addition, insulin receptor aggregation occurs in response to ligand binding and aggregation may also influence binding kinetics. In this study, we develop a mathematical model for insulin receptor binding kinetics that explicitly represents the divalent nature of the insulin receptor and incorporates receptor aggregation into the kinetic model. Model parameters are based upon published data. where available. Computer simulations with our model are capable of reproducing both negative and positive cooperativity at the appropriate insulin concentrations. This model may be a useful tool for helping to understand the mechanisms underlying insulin receptor binding and the coupling of receptor binding to downstream signaling events. (C) 2000 Academic Press. [References: 51]
机译：胰岛素的生物作用调节葡萄糖代谢和其他必要的生理功能。胰岛素与其细胞表面受体的结合启动了介导细胞反应的信号转导途径。因此，非常了解胰岛素受体结合动力学的基本机制。有趣的是，在高胰岛素浓度下观察到负的协同相互作用，而在低胰岛素浓度下可能存在正的协同作用。显然，不能通过经典的双分子反应简单地解释胰岛素受体的结合动力学。成熟的胰岛素受体具有能够结合两个胰岛素分子的二聚体结构。受体对第二胰岛素分子的结合亲和力明显低于对第一结合胰岛素分子的结合亲和力。另外，胰岛素受体聚集响应配体结合而发生，并且聚集也可能影响结合动力学。在这项研究中，我们开发了胰岛素受体结合动力学的数学模型，该模型明确表示了胰岛素受体的二价性质，并将受体聚集纳入动力学模型。模型参数基于已发布的数据。如果有的话。使用我们的模型进行的计算机模拟能够在适当的胰岛素浓度下产生负和正协同性。该模型可能是帮助了解胰岛素受体结合的基本机制以及受体结合与下游信号传导事件耦合的有用工具。 （C）2000学术出版社。 [参考：51]

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