tailieunhanh - Báo cáo y học: " A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets Peter Buchwald"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: " A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets Peter Buchwald | Buchwald Theoretical Biology and Medical Modelling 2011 8 20 http content 8 1 20 THEORETICAL BIOLOGY AND MEDICAL MODELLING RESEARCH Open Access A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets Peter Buchwald Correspondence pbuchwald@med. Diabetes Research Institute and the Department of Molecular and Cellular Pharmacology University of Miami Miller Schoolof Medicine Miami FL USA 2 BioMed Central Abstract Background Because insulin is the main regulator of glucose homeostasis quantitative models describing the dynamics of glucose-induced insulin secretion are of obvious interest. Here a computational model is introduced that focuses not on organism-level concentrations but on the quantitative modeling of local cellular-level glucose-insulin dynamics by incorporating the detailed spatial distribution of the concentrations of interest within isolated avascular pancreatic islets. Methods All nutrient consumption and hormone release rates were assumed to follow Hill-type sigmoid dependences on local concentrations. Insulin secretion rates depend on both the glucose concentration and its time-gradient resulting in second-and first-phase responses respectively. Since hypoxia may also be an important limiting factor in avascular islets oxygen and cell viability considerations were also built in by incorporating and extending our previous islet cell oxygen consumption model. A finite element method FEM framework is used to combine reactive rates with mass transport by convection and diffusion as well as fluidmechanics. Results The model was calibrated using experimental results from dynamic glucose-stimulated insulin release GSIR perifusion studies with isolated islets. Further optimization is still needed but calculated insulin responses to stepwise increments in the incoming glucose concentration are in good agreement with existing experimental insulin release data characterizing glucose and oxygen .