The Interaction of Calcium and Metabolic Oscillations in Pancreatic β-cells

Abstract

Diabetes is a disease characterized by an excessive level of glucose in the blood-stream, which may be a result of improper insulin secretion. Insulin is secreted in a bursting behavior of pancreatic β-cells in the islets of Langerhans, which is affected by oscillations of cytosolic calcium concentration. We used the Dual Oscillator Model to explore the role of calcium in calcium oscillation independent and calcium oscillation dependent (CaD) modes as well as the synchronization of metabolic oscillations in electrically coupled β-cells. We also implemented a synchronization index in order to better measure the synchronization of the β-cells within an islet. We observed that voltage or calcium coupling result in increased synchronization and are more effective in CaD modes. Furthermore, we studied heterogeneous modes of coupled β-cells, their arrangements in the islets, and their synchronization. We saw that increasing calcium coupling or increasing voltage coupling in heterogeneous cases increases synchronization; however, in certain cases increasing both voltage and calcium coupling causes desynchronization, primarily in voltage. To better represent an entire islet, we altered previous code by further optimizing run-time and memory usage to allow for a greater number of cells to be simulated for a longer period of time.