Pancreatic α and β cells are globally phase-locked.

Abstract

The Ca²⁺ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells play a crucial role in glucose homeostasis. However, how α and β cells coordinate to produce various Ca²⁺ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice, we recorded Ca²⁺ signals from islet α and β cells, and observed heterogeneous Ca²⁺ oscillation patterns intrinsic to each islet. After a brief period of glucose stimulation, α and β cells' oscillations were globally phase-locked. While the activation of α cells displayed a fixed time delay of ~20 s to that of β cells, β cells activated with a tunable period. Moreover, islet α 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.