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.
Chew
Yin Hoon
YH
Department of Bioprocess Engineering, Faculty of Chemical and Natural Resources Engineering, Universiti Teknologi Malaysia, Skudai, Johor, Malaysia.
Shia
Yoke Lin
YL
Lee
Chew Tin
CT
Majid
Fadzilah Adibah Abdul
FA
Chua
Lee Suan
LS
Sarmidi
Mohamad Roji
MR
Aziz
Ramlan Abdul
RA
D000465:Algorithms; D001692:Biological Transport; D025461:Feedback, Physiological; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008954:Models, Biological; D015398:Signal Transduction
D051275:Glucose Transporter Type 4; D007328:Insulin; D005947:Glucose