Pancreatic α and β cells are globally phase-locked.

Pancreatic α and β cells are globally phase-locked.
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胰腺α和β细胞全局锁相

DOI:
10.1038/s41467-022-31373-6
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发表时间:
2022-06-28
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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Ca~(2+)调节的胰α和β细胞分泌胰高血糖素和胰岛素的脉动在葡萄糖稳态中起着至关重要的作用。然而,α和β细胞如何协调产生各种Ca2+振荡模式仍然是难以捉摸的。使用微流控装置和转基因小鼠,我们记录了胰岛α和β细胞的Ca2+信号,并观察到每个胰岛固有的异质性Ca2+振荡模式。在短暂的葡萄糖刺激后,α和β细胞的振荡被全局锁相。α细胞的激活相对于β细胞的激活呈现出约20 s的固定时间延迟,而β细胞的激活具有可调的周期。胰岛α细胞数与振荡频率相关。我们建立了一个包含旁分泌相互作用的胰岛Ca~(2+)振荡的数学模型,该模型定量地与实验数据相吻合。我们的研究强调了细胞间相互作用在产生稳定但可调的胰岛振荡模式中的重要性。Ca2+调节胰腺α和β细胞的胰高血糖素和胰岛素分泌的脉动在葡萄糖稳态中是至关重要的。在这里,作者表明α和β细胞的Ca2+振荡是锁相的,并且振荡模式是由α和β细胞之间的旁分泌相互作用调节的。
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. The Ca2+ modulated pulsatile glucagon and insulin secretions by pancreatic α and β cells are critical in glucose homeostasis. Here the authors show that the Ca2+ oscillations of α and β cells are phase-locked, and that the oscillation pattern is tuned by paracrine interactions between α and β cells.
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