earticle

영어

Many models describing glucose homeostasis in blood stream have been developed to predict the glucose levels after meals for diabetic patients. The minimal model of glucose kinetics was developed using only three differential equations [1] and has been widely employed in clinical studies in spite of its low degree of mechanistic detail. On the other hand, mechanistic model of such a complex system often causes over-parameterization and predicts the metabolic
dynamics only under limited conditions. In this study, cybernetic principle condensing sophisticated regulations in metabolic networks was applied in modeling glucose homeostasis in blood stream in the presence of periodical supply of glucose and fat as diet. The mechanistic role of glucokinase was revealed as a metabolic glucose sensor [2], which was simulated by employing the matching law and proportional law in a cybernetic model composed of
major biochemical reactions including glycogen formation/hydrolysis and lipid synthesis/degradation. The objective function was designed to maximize the rate of glucose metabolism in the model and stoichiometric parameters were obtained from the elementary mode analysis of the liver metabolic network. The model fits well with the profiles of blood glucose, fatty acid and triglyceride during glucose tolerance test. It also showed a robust glucose homeostasis under randomized supply of either high-carbohydrate or high-fat diet over a long period of time. An extended model including other organs such as adipose
tissue and muscle is under development to simulate the metabolic dynamics caused by environmental perturbations, for example, drug, disease or exercise.