Pancreatic alpha and beta cells are globally phase-locked

The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic alpha and beta cells play a crucial role in glucose homeostasis. However, how alpha and beta cells coordinate to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca2+ signals from islet alpha and beta cells, and observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, alpha and beta cells' oscillations were globally phase-locked. While the activation of alpha cells displayed a fixed time delay of similar to 20 s to that of beta cells, beta cells activated with a tunable period. Moreover, islet a cell number correlated with oscillation frequency. We built a mathematical model of islet Ca2+ oscillation incorporating paracrine interactions, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction in generating stable but tunable islet oscillation patterns.