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bioRxiv · 10.1101/2020.08.16.252304

Pancreatic α and β cells are globally phase-locked

Ren, H.·Li, Y.·Yu, Y.·Shi, B.·Peng, X.·Wu, S.·Zhu, W.·Yang, G.·Yang, X.·sneppen, k.·Chen, L.·Tang, C.
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Abstract

The Ca2+ modulated pulsatile secretion of glucagon and insulin by pancreatic and {beta} cells plays a key role in glucose homeostasis. However, how and {beta} cells coordinate via paracrine interaction to produce various Ca2+ oscillation patterns is still elusive. Using a microfluidic device and transgenic mice in which and {beta} cells were labeled with different colors, we were able to record islet Ca2+ signals at single cell level for long times. Upon glucose stimulation, we observed heterogeneous Ca2+ oscillation patterns intrinsic to each islet. After a transient period, the oscillations of and {beta} cells were globally phase-locked, i.e., the two types of cells in an islet each oscillate synchronously but with a phase shift between the two. While the activation of cells displayed a fixed time delay of ~20 s to that of {beta} cells, {beta} cells activated with a tunable delay after the cells. As a result, the tunable phase shift between and {beta} cells set the islet oscillation period and pattern. Furthermore, we demonstrated that the phase shift can be modulated by glucagon. A mathematical model of islet Ca2+ oscillation taking into consideration of the paracrine interaction was constructed, which quantitatively agreed with the experimental data. Our study highlights the importance of cell-cell interaction to generate stable but tunable islet oscillation patterns.

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Ren, H., Li, Y., Yu, Y., Shi, B., Peng, X., Wu, S., Zhu, W., Yang, G., Yang, X., sneppen, k., Chen, L., Tang, C.. 2020-08-17. Pancreatic α and β cells are globally phase-locked. https://doi.org/10.1101/2020.08.16.252304

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