  Pancreatic beta cells are coupled excitable oscillators that synchronize
their activity via different communication pathways. Their oscillatory activity
manifests itself on multiple timescales and consists of bursting electrical
activity, subsequent oscillations in the intracellular Ca2+, as well as
oscillations in metabolism and exocytosis. The coordination of the intricate
activity on the multicellular level plays a key role in the regulation of
physiological pulsatile insulin secretion and is incompletely understood. In
this contribution, we investigate theoretically the principles that give rise
to the synchronized activity of beta cell populations by building up a
phenomenological multicellular model that incorporates the basic features of
beta cell dynamics. Specifically, the model is composed of coupled slow and
fast oscillatory units that reflect metabolic processes and electrical
activity, respectively. Using a realistic description of the intercellular
interactions, we study how the combination of electrical and metabolic coupling
generates collective rhythmicity and shapes functional beta cell networks. It
turns out that while electrical coupling solely can synchronize the responses,
the addition of metabolic interactions further enhances coordination, the
spatial range of interactions, increases the number of connections in the
functional beta cell networks, and ensures a better consistency with
experimental findings. Moreover, our computational results provide additional
insights into the relationship between beta cell heterogeneity, their activity
profiles, and functional connectivity, supplementing thereby recent
experimental results on endocrine networks.
