Department of Medicine, University of Chicago, Chicago, IL, USA.
Islets. 2013 Jan-Feb;5(1):1-15. doi: 10.4161/isl.24166.
In mammals an increase in glucose leads to block of ATP dependent potassium channels in pancreatic β cells leading to membrane depolarization. This leads to the repetitive firing of action potentials that increases calcium influx and triggers insulin granule exocytosis. Several important differences between species in this process suggest that a dedicated human-oriented approach is advantageous as extrapolating from rodent data may be misleading in several respects. We examined depolarization-induced spike activity in pancreatic human islet-attached β-cells employing whole-cell patch-clamp methods. We also reviewed the literature concerning regulation of insulin secretion by channel activity and constructed a data-based computer model of human β cell function. The model couples the Hodgkin-Huxley-type ionic equations to the equations describing intracellular Ca²⁺ homeostasis and insulin release. On the basis of this model we employed computational simulations to better understand the behavior of action potentials, calcium handling and insulin secretion in human β cells under a wide range of experimental conditions. This computational system approach provides a framework to analyze the mechanisms of human β cell insulin secretion.
在哺乳动物中，葡萄糖的增加会导致胰腺β细胞中 ATP 依赖性钾通道的阻断，从而导致膜去极化。这导致动作电位的重复发射增加钙内流并触发胰岛素颗粒胞吐。在这个过程中，物种之间存在几个重要的差异，这表明采用专门针对人类的方法是有利的，因为从啮齿动物数据推断可能会在几个方面产生误导。我们采用全细胞膜片钳方法研究了胰腺人胰岛附着β细胞中去极化诱导的尖峰活动。我们还回顾了有关通道活动调节胰岛素分泌的文献，并构建了基于数据的人类β细胞功能计算机模型。该模型将 Hodgkin-Huxley 型离子方程与描述细胞内 Ca²⁺稳态和胰岛素释放的方程耦合。在此模型的基础上，我们采用计算模拟更好地理解了在广泛的实验条件下人类β细胞中动作电位、钙处理和胰岛素分泌的行为。这种计算系统方法为分析人类β细胞胰岛素分泌的机制提供了一个框架。
