Investigating Oscillation Loss in Computational Islets

Abstract

The study of pancreatic β -cells comprises a crucial part of the study of the group of diseases known as diabetes. These cells exist in groups known as islets of Langerhans and are responsible for storing and producing insulin. They exhibit electrical bursting behavior during insulin production that correlates with the rate at which insulin is secreted into the bloodstream. Coupling is a natural process within islets that enables the cells to communicate with one another and transfer various ions and electrical currents; coupling of both voltage and metabolites can occur. We model multicellular islets using an existing system of seven ordinary differential equations to model beta cell function. We first treat metabolic coupling as independent and look for combinations of coupling strengths, initial conditions, and parameter values that lead to metabolic oscillation loss, which has been observed in previous studies using a two-cell model. We find examples of each of these three features that can cause β -cells to exhibit oscillation loss at particular values. Next, we simulate cells with mutated KATP channels that remain open indefinitely, which have been described in experimental studies but not yet modeled. Simulations run with these mutations reveal the existence of a bursting death threshold, described by the least percentage of cells in the islet that must be mutated for electrical bursts to completely disappear. We determine that this threshold is independent of coupling strengths, cell distribution, and possibly islet dimension; however, we also determined that this threshold is not independent of the glucose influx rate.