Dynamical compensation in physiological circuits

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. Ho...

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Bibliographic Details
Published in:Molecular systems biology 2016-11, Vol.12 (11), p.886-n/a
Main Authors: Karin, Omer, Swisa, Avital, Glaser, Benjamin, Dor, Yuval, Alon, Uri
Format: Article
Language:English
Subjects:
Adaptation
Adaptation, Physiological
Blood glucose
calcium homeostasis
Circuits
Compensation
Control theory
Dynamic response
dynamical compensation
endocrine circuits
Feedback
Feedback loops
Feedback, Physiological
glucose homeostasis
Growth rate
Homeostasis
Insulin
Insulin resistance
mathematical models of disease
Models, Biological
Nonlinear feedback
Parameters
Physiology
Response time
Response time (computers)
Robustness
Systems Biology - methods
Variation
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Summary: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. Synopsis Physiological circuits must keep their output dynamics precise despite wide variation in circuit parameters. We present a design principle for this robustness, find that it explains experimental observations on glucose homeostasis, and show that it may apply to other physiological circuits. Dynamical compensation (DC) is precise output dynamics despite variation in parameters. A design principle and sufficient conditions for DC is presented. Glucose regulation by beta‐cell functional mass has DC. Other physiological circuits have the hallmarks of DC. Physiological circuits must keep their output dynamics precise despite wide variation in circuit parameters. We present a design principle for this robustness, find that it explains experimental observations on glucose homeostasis, and show that it may apply to other physiological circuits.
ISSN:1744-4292
1744-4292
DOI:10.15252/msb.20167216