2011 - CTS-IXA


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Parallel Session 20- Encapsulation (Cell Track)

35.531 - A detailed insulin secretion model for encapsulated islets that incorporates oxygen dependence and spatial distribution information

Presenter: Peter, Buchwald, Miami, United States
Authors: Peter Buchwald1

531

A detailed insulin secretion model for encapsulated islets that incorporates oxygen dependence and spatial distribution information

Peter Buchwald

Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, FL, United States

 

Accurate quantitative models of glucose-induced insulin secretion that also incorporate oxygen dependence are of critical value in the design of improved bioartificial pancreas systems, such as those using immune-isolated, encapsulated islets, because oxygen diffusion limitations are a major problem hindering their functionality. We have recently developed a detailed computational model of insulin secretion in avascular islets (Theor. Biol. Med. Model2011, in press) that couples local consumption and release rates to calculations of the spatial distributions of all species of interest by using a finite element method (FEM) framework (COMSOL Multiphysics). Insulin secretion rates were assumed to depend on both the local glucose concentration and its time-gradient, resulting in second- and first-phase responses, respectively, and the model was calibrated using experimental results from dynamic glucose-stimulated insulin release (GSIR) perifusion studies with isolated islets. Following parameterization, good fit could be obtained with experimental perifusion data of human islets (i.e., staircase experiment). With the model, it is now possible to obtain detailed estimates of the intraislet spatial distributions of insulin, glucose, and oxygen concentrations; and because of the general framework of the implementation, simulations can be carried out for arbitrary geometries of avascular islets including cultured, perifused, transplanted, as well as encapsulated islets. In agreement with recent observations, calculations suggest that smaller islets perform better when transplanted and/or encapsulated because of less severe hypoxia in their core regions. At lower oxygen concentrations, such as those that transplanted islets are likely to encounter even in well-vascularized tissues ( pO2 = 35–45 mmHg; coxy= 0.05–0.065 mM), encapsulated islets loose more of their insulin secreting ability than free islets because they suffer more heavily from hypoxia as oxygen diffusion limitations severely restrict the hormone secreting ability of their core regions even with relatively thin microcapsule sizes.


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