δ-α cell-to-cell interactions modulate pancreatic islet Ca2+ oscillation modes

Glucose-induced pancreatic islet hormone release is tightly coupled with oscillations in cytoplasmic free Ca ²⁺ concentration of islet cells, which is regulated by a complex interplay between intercellular and intracellular signaling. δ cells, which entangle with α cells located at the islet periphery, are known to be important paracrine regulators. However, the role of δ cells in regulating Ca ²⁺ oscillation pattern remains unclear. Here we show that δ-α cell-to-cell interactions are the source of variability in glucose-induced Ca ²⁺ oscillation pattern. Somatostatin secreted from δ cells prolonged the islet’s oscillation period in an α cell mass-dependent manner. Pharmacological and optogenetic perturbations of δ-α interactions led islets to switch between fast and slow Ca ²⁺ oscillations. Continuous adjustment of δ-α coupling strength caused the fast oscillating islets to transition to mixed and slow oscillations. We developed a mathematical model, demonstrating that the fast-mixed-slow oscillation transition is a Hopf bifurcation. Our findings provide a comprehensive understanding of how δ cells modulate islet Ca ²⁺ dynamics and reveal the intrinsic heterogeneity of islets due to the structural composition of different cell types.