A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets
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RESEARCH
Open Access
A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets Peter Buchwald Correspondence: pbuchwald@med. miami.edu Diabetes Research Institute and the Department of Molecular and Cellular Pharmacology, University of Miami, Miller School of Medicine, Miami, FL, USA
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, cellularlevel 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 glucosestimulated 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 dependence. The model makes possible the detailed description of the intraislet spatial distributions of insulin, glucose, and oxygen levels. In agreement with recent observations, modeling also suggests that smaller islets perform better when transplanted and/or encapsulated. Conclusions: An insulin secretion model was implemented by coupling local consumption and release rates to calculations of the spatial distributions of all species of interest. The resulting glucose-insulin control system fits in the general framework of a sigmoid proportional-integral-derivative controller, a generalized PID controller, more suitable for biological systems, which are always nonlinear due to the maximum response being limited. Because of the general framework of the implementation, simulations can be carried out for arbitrary geometries including cultured, perifused, transplanted, and encapsulated islets. Keywords: diabetes mellitus, FEM model, glucose-insulin dynamics, Hill equation, islet perifusion, islets of Langerhans, oxygen consumption, PID controller
© 2011 Buchwald; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Li
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