A calcium-based phantom bursting model for pancreatic islets
A calcium-based phantom bursting model for pancreatic islets
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DOI：
10.1016/j.bulm.2003.12.005
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发表时间：
2004-09-01
影响因子：
3.5
通讯作者：
Sherman, A
中科院分区：
文献类型：
--
作者：
Bertram, R;Sherman, A
胰岛素分泌β细胞位于胰岛内，是可逃避的细胞，当受到葡萄糖刺激时产生有规律的动作电位爆发。二十年来，这个系统一直是数学研究的焦点，产生了一系列数学模型。最近，已经引入了一类新的模型，称为“幻影爆发器”[Bertram等人（2000）Biophys. J. 79.2880-2892]，这说明了胰岛通过一个以上缓慢过程的相互作用而表现出的宽范围的爆发频率。在这里，我们描述了一个实现的幻影爆裂机制，其中细胞内的Ca 2+控制振荡通过直接和间接的负反馈途径。我们展示了如何通过扩展通常用于突发振荡的快/慢分析来理解模型动态。从这个角度来看，该模型利用多个自由度来产生β细胞所表现出的全范围的爆发振荡。该模型还占了广泛的实验现象，包括无处不在的三相响应的葡萄糖的阶跃升高和响应内部Ca 2+商店的扰动。虽然它目前还不是一个完整的模型，所有β细胞的属性，它表明了设计原则，我们预计将在β细胞建模的未来进展。
Insulin-secreting beta-cells, located within the pancreatic islets of Langerhan,are escitable cells that produce regular bursts of action potentials when stimulated by glucose. This system has been the focus of mathematical investigation for two decades, spawning an array of mathematical models. Recectly, a new class of models has been introduced called 'phantom bursters' [Bertram et al. (2000) Biophys. J. 79.2880-2892], which acounts for the wide range of burst frequencies exhibited by islets via interaction of more than one slow process. Here, we describe one implementation of the phantom bursting mechanism in which intracellular Ca2+ controls the oscillations through both direct and indirect negative feedback pathways. We show how the model dynamics can be understood through an extension of the fast/slow analysis that is typically employed for bursting oscillations. From this perspective, the model makes use of multiple degrees of freedom to generate the full range of bursting oscillations exhibited by beta-cells. The model also accounts for a wide range of experimental phenomena, including the ubiquitous triphasic response to the step elevation of glucose and responses to perturbations of internal Ca2+ stores. Although it is not presently a complete model of all beta-cell properties it demonstrates the design principles that we anticipate will underlie future progress in beta-cell modeling.