Symbiosis of Electrical and Metabolic Oscillations in Pancreatic β-Cells.
Symbiosis of Electrical and Metabolic Oscillations in Pancreatic β-Cells.
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DOI：
10.3389/fphys.2021.781581
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发表时间：
2021
影响因子：
4
通讯作者：
Bertram R
中科院分区：
文献类型：
--
作者：
Marinelli I;Fletcher PA;Sherman AS;Satin LS;Bertram R
胰岛素以脉动模式分泌，具有重要的生理影响。在胰腺 β 细胞（合成胰岛素的细胞）中，胰岛素胞吐作用是由电活动爆发引发的细胞内 Ca2+ 升高的脉冲引起的。与这些电振荡和 Ca2+ 振荡并行的是新陈代谢的振荡，并且所有这些振荡过程的周期都是相似的。一个尚未解决的关键问题是，电振荡是否通过 Ca2+ 的作用导致代谢振荡，或者代谢振荡是否因 ATP 对 ATP 敏感离子通道的影响而导致电振荡？数学建模是解决此问题及相关问题的有用工具，因为建模可以帮助设计重点突出的实验，这些实验可以测试特定模型的预测，并随后用于以迭代方式改进模型。在本文中，我们讨论一个最新的数学模型，即集成振荡器模型 (IOM)，它是多年发展的产物。我们使用该模型来证明β细胞中钙与代谢之间的关系是共生的：在某些情况下，电振荡驱动代谢振荡，而在其他情况下则相反。我们对这些结果提供了新的见解，并说明，当从 IOM 的整体角度来看时，乍一看可能相互矛盾的数据实际上是兼容的。
Insulin is secreted in a pulsatile pattern, with important physiological ramifications. In pancreatic β-cells, which are the cells that synthesize insulin, insulin exocytosis is elicited by pulses of elevated intracellular Ca2+ initiated by bursts of electrical activity. In parallel with these electrical and Ca2+ oscillations are oscillations in metabolism, and the periods of all of these oscillatory processes are similar. A key question that remains unresolved is whether the electrical oscillations are responsible for the metabolic oscillations via the effects of Ca2+, or whether the metabolic oscillations are responsible for the electrical oscillations due to the effects of ATP on ATP-sensitive ion channels? Mathematical modeling is a useful tool for addressing this and related questions as modeling can aid in the design of well-focused experiments that can test the predictions of particular models and subsequently be used to improve the models in an iterative fashion. In this article, we discuss a recent mathematical model, the Integrated Oscillator Model (IOM), that was the product of many years of development. We use the model to demonstrate that the relationship between calcium and metabolism in beta cells is symbiotic: in some contexts, the electrical oscillations drive the metabolic oscillations, while in other contexts it is the opposite. We provide new insights regarding these results and illustrate that what might at first appear to be contradictory data are actually compatible when viewed holistically with the IOM.
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DOI：
10.1085/jgp.201110611
发表时间：
2011-07
期刊：
The Journal of general physiology
影响因子：
--
作者：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1016/j.bbamcr.2015.04.008
发表时间：
2015-09
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
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通讯作者：
Rizzuto R