Pancreatic islets are functional units involved in glucose homeostasis. The
multicellular system comprises three main cell types; β and α
cells reciprocally decrease and increase blood glucose by producing insulin and
glucagon pulses, while the role of δ cells is less clear. Although their
spatial organization and the paracrine/autocrine interactions between them have
been extensively studied, the functional implications of the design principles
are still lacking. In this study, we formulated a mathematical model that
integrates the pulsatility of hormone secretion and the interactions and
organization of islet cells and examined the effects of different cellular
compositions and organizations in mouse and human islets. A common feature of
both species was that islet cells produced synchronous hormone pulses under
low- and high- glucose conditions, while they produced asynchronous hormone
pulses under normal glucose conditions. However, the synchronous coordination
of insulin and glucagon pulses at low glucose was more pronounced in human
islets that had more α cells. When β cells were selectively
removed to mimic diabetic conditions, the anti-synchronicity of insulin and
glucagon pulses was deteriorated at high glucose, but it could be partially
recovered when the re-aggregation of remaining cells was considered. Finally,
the third cell type, δ cells, which introduced additional complexity in
the multicellular system, prevented the excessive synchronization of hormone
pulses. Our computational study suggests that controllable synchronization is a
design principle of pancreatic islets.Comment: 24 pages, 7 figure