Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets
Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets
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DOI：
10.1529/biophysj.106.097154
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Sherman, Arthur
中科院分区：
文献类型：
--
作者：
Bertram, Richard;Satin, Leslie S.;Sherman, Arthur
胰腺β细胞的胰岛素分泌是振荡的，典型周期为2-7分钟，反映了膜电位和胞质Ca2+浓度的振荡。我们的中心假设是，缓慢的 2-7 分钟振荡是由于糖酵解振荡，而叠加的较快振荡是由于 Ca2+ 反馈到代谢或离子通道上。我们基于这一假设扩展了先前的数学模型，以包括对线粒体代谢的更详细描述。我们证明该模型可以解释胰岛中膜电位和 Ca2+ 浓度的典型振荡模式。它还解释了胰岛耗氧量的时间数据。最近对糖酵解振荡驱动胰岛中缓慢 Ca2+ 振荡这一观点的挑战是，数据显示 Ca2+、线粒体耗氧量和 NAD(P)H 水平的振荡均由膜超极化终止。我们证明这些数据实际上与糖酵解振荡是节律性胰岛活动的关键参与者的模型兼容。最后，我们使用该模型来解决最近的发现，即某些小鼠的胰岛活动一致较快，而其他小鼠的胰岛活动较慢。我们提出了一种针对这种二分法的机制。
Insulin secretion from pancreatic beta-cells is oscillatory, with a typical period of 2-7 min, reflecting oscillations in membrane potential and the cytosolic Ca2+ concentration. Our central hypothesis is that the slow 2-7 min oscillations are due to glycolytic oscillations, whereas faster oscillations that are superimposed are due to Ca2+ feedback onto metabolism or ion channels. We extend a previous mathematical model based on this hypothesis to include a more detailed description of mitochondrial metabolism. We demonstrate that this model can account for typical oscillatory patterns of membrane potential and Ca2+ concentration in islets. It also accounts for temporal data on oxygen consumption in islets. A recent challenge to the notion that glycolyfic oscillations drive slow Ca2+ Oscillations in islets are data showing that oscillations in Ca2+, mitochondrial oxygen consumption, and NAD(P)H levels are all terminated by membrane hyperpolarization. We demonstrate that these data are in fact compatible with a model in which glycolytic oscillations are the key player in rhythmic islet activity. Finally, we use the model to address the recent finding that the activity of islets from some mice is uniformly fast, whereas that from islets of other mice is slow. We propose a mechanism for this dichotomy.