Modeling of glucose regulation and insulin-signaling pathways

A model of glucose regulation system was combined with a model of insulin-signaling pathways in this study. A feedback loop was added to link the transportation of glucose into cells (by GLUT4 in the insulin-signaling pathways) and the insulin-dependent glucose uptake in the glucose regulation model using the Michaelis-Menten kinetic model. A value of K-m for GLUT4 was estimated using Genetic Algorithm. The estimated value was found to be 25.3 mM, which was in the range of K-m values found experimentally from in vivo and in vitro human studies. Based on the results of this study, the combined model enables us to understand the overall dynamics of glucose at the systemic level, monitor the time profile of components in the insulin-signaling pathways at the cellular level and gives a good estimate of the K-m value of glucose transportation by GLUT4. In conclusion, metabolic modeling such as displayed in this study provides a good predictive method to study the step-by-step reactions in an organism at different levels and should be used in combination with experimental approach to increase our understanding of metabolic disorders such as type 2 diabetes. (C) 2009 Elsevier Ireland Ltd. All rights reserved.