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Publication Detail
A composite computational model of liver glucose homeostasis. I. Building the composite model.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Hetherington J, Sumner T, Seymour RM, Li L, Rey MV, Yamaji S, Saffrey P, Margoninski O, Bogle ID, Finkelstein A, Warner A
  • Publication date:
    07/04/2012
  • Pagination:
    689, 700
  • Journal:
    J R Soc Interface
  • Volume:
    9
  • Issue:
    69
  • Status:
    Published
  • Country:
    England
  • PII:
    rsif.2011.0141
  • Language:
    eng
  • Keywords:
    Algorithms, Animals, Calcium Signaling, Cyclic AMP, Feedback, Physiological, Glucose, Glycogenolysis, Homeostasis, Humans, Insulin, Liver, Liver Circulation, Liver Glycogen, Models, Biological, Pancreas, Rats, Receptors, Glucagon, Signal Transduction, Systems Biology
Abstract
A computational model of the glucagon/insulin-driven liver glucohomeostasis function, focusing on the buffering of glucose into glycogen, has been developed. The model exemplifies an 'engineering' approach to modelling in systems biology, and was produced by linking together seven component models of separate aspects of the physiology. The component models use a variety of modelling paradigms and degrees of simplification. Model parameters were determined by an iterative hybrid of fitting to high-scale physiological data, and determination from small-scale in vitro experiments or molecular biological techniques. The component models were not originally designed for inclusion within such a composite model, but were integrated, with modification, using our published modelling software and computational frameworks. This approach facilitates the development of large and complex composite models, although, inevitably, some compromises must be made when composing the individual models. Composite models of this form have not previously been demonstrated.
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