Karin Omer, Swisa Avital, Glaser Benjamin, Dor Yuval, Alon Uri
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Department of Developmental Biology and Cancer Research and Molecular Biology, The Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Mol Syst Biol. 2016 Nov 8;12(11):886. doi: 10.15252/msb.20167216.
Biological systems can maintain constant steady-state output despite variation in biochemical parameters, a property known as exact adaptation. Exact adaptation is achieved using integral feedback, an engineering strategy that ensures that the output of a system robustly tracks its desired value. However, it is unclear how physiological circuits also keep their output dynamics precise-including the amplitude and response time to a changing input. Such robustness is crucial for endocrine and neuronal homeostatic circuits because they need to provide a precise dynamic response in the face of wide variation in the physiological parameters of their target tissues; how such circuits compensate their dynamics for unavoidable natural fluctuations in parameters is unknown. Here, we present a design principle that provides the desired robustness, which we call dynamical compensation (DC). We present a class of circuits that show DC by means of a nonlinear feedback loop in which the regulated variable controls the functional mass of the controlling endocrine or neuronal tissue. This mechanism applies to the control of blood glucose by insulin and explains several experimental observations on insulin resistance. We provide evidence that this mechanism may also explain compensation and organ size control in other physiological circuits.
尽管生化参数存在变化,生物系统仍能维持恒定的稳态输出,这一特性被称为精确适应。精确适应是通过积分反馈实现的,这是一种工程策略,可确保系统输出稳健地跟踪其期望值。然而,尚不清楚生理回路如何保持其输出动态精确,包括对变化输入的幅度和响应时间。这种稳健性对于内分泌和神经元稳态回路至关重要,因为它们需要在其靶组织的生理参数存在广泛变化的情况下提供精确的动态响应;此类回路如何针对参数中不可避免的自然波动来补偿其动态仍不清楚。在此,我们提出一种提供所需稳健性的设计原则,我们称之为动态补偿(DC)。我们展示了一类通过非线性反馈回路表现出DC的回路,其中调节变量控制着控制内分泌或神经元组织的功能质量。这种机制适用于胰岛素对血糖的控制,并解释了关于胰岛素抵抗的若干实验观察结果。我们提供证据表明,这种机制也可能解释其他生理回路中的补偿和器官大小控制。