Investigating How Calcium Diffusion Affects Metabolic Oscillations and Synchronization of Pancreatic Beta Cells

Abstract

Diabetes is a disease characterized by improper concentrations of blood glucose due to irregular insulin production or sensitivity. Coupled in islets of Langerhans within the pancreas, β-cells are responsible for the production and regulation of insulin based on changes in glucose levels. Using the Dual Oscillator Model (DOM), we will examine how calcium handling between individual pancreatic β-cells affects the synchronization of metabolic oscillations within electrically coupled islets. Calcium permeability was implemented into the DOM, and numerical solutions of the system were obtained via MATLAB using a modified ordinary differential equation solver for stiff systems and the Automatic Differentiation for MATLAB software. We developed a synchronization index to quantitatively describe the synchronization of variables between nearest neighboring cells and throughout the islet as a whole. We considered how calcium permeability between heterogeneous cells affects the behavior of metabolic oscillations and their synchronization. In particular, we examined fructose-1, 6-bisphosphate. In our study metabolic oscillations were always maintained. We also showed that, for low to moderate levels of electrical coupling, calcium permeability increased the synchronization index, but increasing calcium permeability had little effect on synchronization when cells were already strongly synchronized with strong electrical coupling. Heterogeneity due to glucose influx or initial state of the cells had similar synchronization results.