Synchronization of Pancreatic Islet Oscillations by Intrapancreatic Ganglia: A Modeling Study
Synchronization of Pancreatic Islet Oscillations by Intrapancreatic Ganglia: A Modeling Study
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DOI：
10.1016/j.bpj.2009.05.016
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发表时间：
2009-08-05
影响因子：
3.4
通讯作者：
Bertram, R.
中科院分区：
文献类型：
--
作者：
Fendler, B.;Zhang, M.;Bertram, R.
小鼠、大鼠、狗和人类的血浆胰岛素测量结果表明，胰岛素水平是振荡的，反映了各个胰岛的脉动胰岛素分泌。然而，一个悬而未决的问题是，胰岛群的活动如何协调以产生血浆胰岛素的相干振荡。在这里，我们使用数学模型研究了潜在的胰岛同步机制（胆碱能信号传导）的可行性。这一假设基于证实胰腺内副交感神经（胆碱能）神经节的充分实验证据，以及最近的体外证据，即短暂应用毒蕈碱激动剂可以暂时同步胰岛。我们使用数学模型证明，胆碱能神经元释放的乙酰胆碱的周期性脉冲确实能够协调模拟胰岛群的活动，即使其中只有一小部分受到神经支配。还考虑了胰岛间异质性的作用。结果表明，胰腺胆碱能输入的存在可能充当体内内源性胰岛素脉动的调节剂。
Plasma insulin measurements from mice, rats, dogs, and humans indicate that insulin levels are oscillatory, reflecting pulsatile insulin secretion from individual islets. An unanswered question, however, is how the activity of a population of islets is coordinated to yield coherent oscillations in plasma insulin. Here, using mathematical modeling, we investigate the feasibility of a potential islet synchronization mechanism, cholinergic signaling. This hypothesis is based on well-established experimental evidence demonstrating intrapancreatic parasympathetic (cholinergic) ganglia and recent in vitro evidence that a brief application of a muscarinic agonist can transiently synchronize islets. We demonstrate using mathematical modeling that periodic pulses of acetylcholine released from cholinergic neurons is indeed able to coordinate the activity of a population of simulated islets, even if only a fraction of these are innervated. The role of islet-to-islet heterogeneity is also considered. The results suggest that the existence of cholinergic input to the pancreas may serve as a regulator of endogenous insulin pulsatility in vivo.