Glucose-driven intra- and inter-islet beta cell synchronization in pancreatic tissue slices

Coordinated insulin secretion by the numerous islets dispersed throughout the pancreas generates the characteristic pulsatility of circulating insulin, which optimizes peripheral insulin action. While intra-islet communication is well established, the mechanisms supporting inter-islet coordination remain unclear. We investigated how different glucose stimulation patterns influence beta cell calcium dynamics across neighboring islets using multicellular calcium imaging in acute pancreatic tissue slices from NMRI mice, each containing two spatially separated islets. We compared islet responses under constant glucose stimulation and under periodic glucose pulses at either low amplitude or high amplitude. Fast, electrically driven oscillations showed no inter-islet alignment under any protocol but consistently exhibited strong coherence within each islet's beta cell syncytium. The slow, metabolically driven component showed poor inter-islet coordination during constant glucose stimulation and under low-amplitude pulsations centered near 10 mM, but displayed partial alignment with low-amplitude pulses near the physiological range (8 mM). Robust inter-islet synchronization emerged only under high-amplitude glucose oscillations. These findings demonstrate that periodic glucose input can entrain slow β-cell rhythms across islets. However, because physiological glucose fluctuations are modest, such entrainment is unlikely to fully explain inter-islet coordination in vivo, suggesting that additional mechanisms support coherent, pulsatile insulin release at the whole-organ level.