Computational Model for Studying the Analogies Between Endocrine Systems of Humans and Rats with Diabetes Mellitus. Experimental and Simulated Results.

Abstract As a common laboratory practice, rats are studied as biological models for understanding human endocrine behavior. However, up to now there is not a computational model of these mammals because adjusting a physiological model of the endocrine system is not an easy task. Thus, in this work the first mathematical model of the interaction between insulin and glucose in diabetic rats available to the scientific community is presented. It is based on the diabetic patient model accepted by the FDA in 2008. However, it has a large number of parameters, being most of them very difficult to determine in real patients. The main idea is to obtain a proper in silico diabetic rat which would be able to compare well with the experimental data. It will provide interesting insight about the analogies with humans and, in future, analyze the possibility of doing a realistic scale-up between both, humans and rats. Therefore, the list of model equations and the corresponding parameters, obtained by specific experiments, are described and tested with the simulated results.

[1]  Claudio Cobelli,et al.  Meal Simulation Model of the Glucose-Insulin System , 2007, IEEE Transactions on Biomedical Engineering.

[2]  C. Cobelli,et al.  In Silico Preclinical Trials: A Proof of Concept in Closed-Loop Control of Type 1 Diabetes , 2009, Journal of diabetes science and technology.

[3]  C. Cobelli,et al.  A physiological simulation model of the glucose-insulin system , 1999, Proceedings of the First Joint BMES/EMBS Conference. 1999 IEEE Engineering in Medicine and Biology 21st Annual Conference and the 1999 Annual Fall Meeting of the Biomedical Engineering Society (Cat. N.

[4]  A M Albisser,et al.  A circulation and organs model for insulin dynamics. , 1979, The American journal of physiology.

[5]  A. Rigalli,et al.  Experimental Surgical Models in the Laboratory Rat , 2009 .

[6]  Bart De Moor,et al.  DEVELOPMENT OF A CRITICALLY ILL PATIENT INPUT-OUTPUT MODEL , 2006 .

[7]  Anirban Roy,et al.  DYNAMIC MODELING OF FREE FATTY ACID, GLUCOSE, AND INSULIN DURING REST AND EXERCISE IN INSULIN DEPENDENT DIABETES MELLITUS PATIENTS , 2008 .

[8]  W Kenneth Ward,et al.  A novel insulin delivery algorithm in rats with type 1 diabetes: the fading memory proportional-derivative method. , 2005, Artificial organs.

[9]  R.S. Parker,et al.  A model-based algorithm for blood glucose control in Type I diabetic patients , 1999, IEEE Transactions on Biomedical Engineering.

[10]  E. H. Twizell.  The mathematical modeling of metabolic and endocrine systems: E.R. Carson, C. Cobelli and L. Finkelstein John Wiley and Sons, Chichester, Sussex, UK, 394 pp., £45.15, 1983 , 1984 .

[11]  F. Stahl.  Diabetes Mellitus Modelling Based on Blood Glucose Measurements , 2003 .

[12]  R. Gleason,et al.  A Model of Glucose-insulin Homeostasis in Man that Incorporates the Heterogeneous Fast Pool Theory of Pancreatic Insulin Release , 1978, Diabetes.

[13]  John Thomas Sorensen,et al.  A physiologic model of glucose metabolism in man and its use to design and assess improved insulin therapies for diabetes , 1985 .

[14]  R. Bergman,et al.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. , 1981, The Journal of clinical investigation.