Geometric analysis of mixed-mode oscillations in a model of electrical activity in human beta-cells

Human pancreatic beta-cells may exhibit complex mixed-mode oscillatory electrical activity, which underlies insulin secretion. A recent biophysical model of human beta-cell electrophysiology can simulate such bursting behavior, but a mathematical understanding of the model’s dynamics is still lacking. Here we exploit time-scale separation to simplify the original model to a simpler three-dimensional model that retains the behavior of the original model and allows us to apply geometric singular perturbation theory to investigate the origin of mixed-mode oscillations. Changing a parameter modeling the maximal conductance of a potassium current, we find that the reduced model possesses a singular Hopf bifurcation that results in small-amplitude oscillations, which go through a period-doubling sequence and chaos until the birth of a large-scale return mechanism and bursting dynamics. The theory of folded node singularities provide insight into the bursting dynamics further away from the singular Hopf bifurcation and the eventual transition to simple spiking activity. Numerical simulations confirm that the insight obtained from the analysis of the reduced model can be lifted back to the original model.