A Generic Integrated Physiologically based Whole‐body Model of the Glucose‐Insulin‐Glucagon Regulatory System
Open Access
- 14 August 2013
- journal article
- research article
- Published by Wiley in CPT: Pharmacometrics & Systems Pharmacology
- Vol. 2 (8), 1-10
- https://doi.org/10.1038/psp.2013.40
Abstract
Models of glucose metabolism are a valuable tool for fundamental and applied medical research in diabetes. Use cases range from pharmaceutical target selection to automatic blood glucose control. Standard compartmental models represent little biological detail, which hampers the integration of multiscale data and confines predictive capabilities. We developed a detailed, generic physiologically based whole‐body model of the glucose‐insulin‐glucagon regulatory system, reflecting detailed physiological properties of healthy populations and type 1 diabetes individuals expressed in the respective parameterizations. The model features a detailed representation of absorption models for oral glucose, subcutaneous insulin and glucagon, and an insulin receptor model relating pharmacokinetic properties to pharmacodynamic effects. Model development and validation is based on literature data. The quality of predictions is high and captures relevant observed inter‐ and intra‐individual variability. In the generic form, the model can be applied to the development and validation of novel diabetes treatment strategies. CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e65; doi:10.1038/psp.2013.40; published online 14 August 2013Keywords
This publication has 51 references indexed in Scilit:
- First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug developmentJournal of Pharmacokinetics and Pharmacodynamics, 2012
- Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculatureAmerican Journal of Physiology-Endocrinology and Metabolism, 2011
- A composite computational model of liver glucose homeostasis. I. Building the composite modelJournal of The Royal Society Interface, 2011
- A Computational Systems Biology Software Platform for Multiscale Modeling and Simulation: Integrating Whole-Body Physiology, Disease Biology, and Molecular Reaction NetworksFrontiers in Physiology, 2011
- A Review of Closed-Loop Algorithms for Glycemic Control in the Treatment of Type 1 DiabetesAlgorithms, 2009
- A simulation model of glucose regulation in the critically illPhysiological Measurement, 2008
- Mathematical modeling and analysis of insulin clearance in vivoBMC Systems Biology, 2008
- Transcriptional feedback control of insulin receptor by dFOXO/FOXO1Genes & Development, 2005
- Modeling the Insulin–Glucose Feedback System: The Significance of Pulsatile Insulin SecretionJournal of Theoretical Biology, 2000
- A mathematical model and computer simulation study of insulin receptor regulationJournal of Theoretical Biology, 1991