TITLE:
Glucose-stimulated insulin secretion in isolated pancreatic islets: Multiphysics FEM model calculations compared to results of perifusion experiments with human islets
AUTHORS:
Peter Buchwald, Sirlene R. Cechin
KEYWORDS:
COMSOL Multiphysics; Diabetes Mellitus; FEM Model; Glucose-Insulin Dynamics; Hill Equation; Islet Perifusion; Islets of Langerhans
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.6 No.5A,
May
28,
2013
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.