Abstract
Because insulin released by the β-cells of pancreatic islets is the main regulator of glucose levels, the quantitative modeling of their glucose-stimulated insulin secretion is of obvious interest not only to improve our understanding of the processes involved, but also to allow better assessment of β -cell function in diabetic patients or islet transplant recipients as well as the development of improved artificial or bioartificial pancreas devices. We have recently developed a general, local concentrations-based multiphysics computational model of insulin secretion in avascular pancreatic islets that can be used to calculate insulin secretion for arbitrary geometries of cultured, perifused, transplanted, or encapsulated islets in response to various glucose profiles. Here, experimental results obtained from two different dynamic glucose-stimulated insulin release (GSIR) perifusion studies performed by us following standard procedures are compared to those calculated by the model. Such perifusion studies allow the quantitative assessment of insulin release kinetics under fully controllable experimental conditions of varying external concentrations of glucose, oxygen, or other compounds of interest, and can provide an informative assessment of islet quality and function. The time-profile of the insulin secretion calculated by the model was in good agree- ment with the experimental results obtained with isolated human islets. Detailed spatial distributions of glucose, oxygen, and insulin were calculated and are presented to provide a quantitative visualization of various important aspects of the insulin secretion dynamics in perifused islets.
Highlights
Quantitative models describing the dynamics of glucosestimulated insulin secretion are of obvious interest [1] for both type 1 [2] and type 2 diabetes mellitus
Because insulin released by the β-cells of pancreatic islets is the main regulator of glucose levels, the quantitative modeling of their glucose-stimulated insulin secretion is of obvious interest to improve our understanding of the processes involved, and to allow better assessment of β-cell function in diabetic patients or islet transplant recipients as well as the development of improved artificial or bioartificial pancreas devices
Experimental results obtained from two different dynamic glucose-stimulated insulin release (GSIR) perifusion studies performed by us following standard procedures are compared to those calculated by the model
Summary
Quantitative models describing the dynamics of glucosestimulated insulin secretion are of obvious interest [1] for both type 1 (insulin-dependent or juvenile-onset) [2] and type 2 (non-insulin dependent or adult-onset) diabetes mellitus. Maintenance of glucose levels within the normal range (typically within 3.5 - 7.0 mM = 60 - 125 mg/ dL in healthy humans) is achieved via the finely-tuned glucose-insulin control system. This mainly relies on cells located in pancreatic islets that act as a glucose sensor and adjust their insulin output as a function of the blood glucose level. Quantitative models of how healthy -cells release insulin in response to a change in glucose levels are of critical importance for many different fields such as, for example: The development of “artificial pancreas” systems [3]. Because of the general FEMbased implementation of the model, simulations can be carried out for arbitrary geometries including cultured, perifused, transplanted, and encapsulated islets [17]
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