Pancreatic islet oscillation rhythmicity arises from δ and α cell interactions

Glucose-stimulated hormone secretion in pancreatic islets is closely linked to oscillations in cytoplasmic Ca²⁺, which arise from complex intra- and intercellular signaling. δ cells, intermingled with peripheral α cells, are important paracrine regulators, but their role in shaping Ca²⁺ oscillations remains unclear. Here, we show that δ-α cell interactions contribute to the variability of glucose-induced Ca²⁺ oscillation patterns. Somatostatin released by δ cells prolonged the oscillation period in an α cell-mass-dependent manner. Pharmacological and optogenetic perturbations of δ-α interactions prompted an oscillation transition. Continuous adjustment of δ-α coupling strength caused the fast-oscillating islets to transition to mixed and slow oscillations. Mathematical modeling indicated that this fast-mixed-slow transition is a Hopf bifurcation. In vivo, blood glucose correlated with oscillation mode: hyperglycemia with slow oscillations and euglycemia with fast oscillations. These findings explain how δ and α cells shape islet Ca²⁺ dynamics, a phenomenon dictated by the diverse cytoarchitecture of the islet. A record of this paper's transparent peer review process is included in the supplemental information.