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胰腺胰岛中的钙与代谢振荡:谁在掌控全局?

Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?.

作者信息

Watts Margaret, Fendler Bernard, Merrins Matthew J, Satin Leslie S, Bertram Richard, Sherman Arthur

机构信息

National Institutes of Health, Bethesda, MD 20892. The first and sixth authors' research was supported by the NIH/NIDDK Intramural Research Program.

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724. This author's research was supported by the Simons Foundation and the Starr Cancer Consortium (I3-A123).

出版信息

SIAM J Appl Dyn Syst. 2014;13(2):683-703. doi: 10.1137/130920198.

Abstract

Pancreatic islets exhibit bursting oscillations in response to elevated blood glucose. These oscillations are accompanied by oscillations in the free cytosolic Ca concentration ( ), which drives pulses of insulin secretion. Both islet Ca and metabolism oscillate, but there is some debate about their interrelationship. Recent experimental data show that metabolic oscillations in some cases persist after the addition of diazoxide (Dz), which opens K(ATP) channels, hyperpolarizing -cells and preventing Ca entry and Ca oscillations. Further, in some islets in which metabolic oscillations were eliminated with Dz, increasing the cytosolic Ca concentration by the addition of KCl could restart the metabolic oscillations. Here we address why metabolic oscillations persist in some islets but not others, and why raising restarts oscillations in some islets but not others. We answer these questions using the dual oscillator model (DOM) for pancreatic islets. The DOM can reproduce the experimental data and shows that the model supports two different mechanisms for slow metabolic oscillations, one that requires calcium oscillations and one that does not.

摘要

胰岛在血糖升高时会出现爆发性振荡。这些振荡伴随着游离胞质钙浓度( )的振荡,后者驱动胰岛素分泌脉冲。胰岛钙和代谢都发生振荡,但其相互关系存在一些争议。最近的实验数据表明,在添加二氮嗪(Dz)后,某些情况下代谢振荡仍会持续,二氮嗪可打开K(ATP)通道,使β细胞超极化并阻止钙进入和钙振荡。此外,在一些用Dz消除代谢振荡的胰岛中,通过添加氯化钾增加胞质钙浓度可重新启动代谢振荡。在这里,我们探讨为什么代谢振荡在某些胰岛中持续而在其他胰岛中不持续,以及为什么提高 在某些胰岛中能重新启动振荡而在其他胰岛中不能。我们使用胰岛的双振荡器模型(DOM)来回答这些问题。DOM可以重现实验数据,并表明该模型支持两种不同的慢代谢振荡机制,一种需要钙振荡,另一种则不需要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4990/4331037/27ceb8190922/nihms661567f1.jpg

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