title: A composite computational model of liver glucose homeostasis. I. Building the composite model.
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.
authors.affiliation: CoMPLEX, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: J
authors.initials: J
authors.lastname: Hetherington
authors.forename: T
authors.initials: T
authors.lastname: Sumner
authors.forename: R M
authors.initials: RM
authors.lastname: Seymour
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: M Varela
authors.initials: MV
authors.lastname: Rey
authors.forename: S
authors.initials: S
authors.lastname: Yamaji
authors.forename: P
authors.initials: P
authors.lastname: Saffrey
authors.forename: O
authors.initials: O
authors.lastname: Margoninski
authors.forename: I D L
authors.initials: ID
authors.lastname: Bogle
authors.forename: A
authors.initials: A
authors.lastname: Finkelstein
authors.forename: A
authors.initials: A
authors.lastname: Warner
mesh_terms: D000465:Algorithms; D000818:Animals; D020013:Calcium Signaling; D000242:Cyclic AMP / Q000378:metabolism; D025461:Feedback, Physiological; D005947:Glucose / Q000378:metabolism*; D050261:Glycogenolysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008112:Liver Glycogen / Q000378:metabolism; D008954:Models, Biological; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism; D015398:Signal Transduction; D049490:Systems Biology
chemical_list: D007328:Insulin; D008112:Liver Glycogen; D018027:Receptors, Glucagon; D000242:Cyclic AMP; D005947:Glucose