A subcellular model of glucose-stimulated pancreatic insulin secretion
A subcellular model of glucose-stimulated pancreatic insulin secretion
复制标题
葡萄糖刺激胰腺胰岛素分泌的亚细胞模型
DOI：
10.1098/rsta.2008.0120
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
C. Cobelli
中科院分区：
文献类型：
--
作者：
M. G. Pedersen;A. Corradin;G. Toffolo;C. Cobelli
当葡萄糖从基础水平升高到刺激水平时，胰岛以典型的双相胰岛素分泌模式响应。此外，胰腺能够识别葡萄糖浓度的变化率。我们提出了一个相对简单的胰腺β细胞分泌胰岛素的模型，但建立在坚实的生理基础上，并能够从灌注的胰腺以及刺激的胰岛中复制一系列分泌模式。该模型包括不同的颗粒池的概念，以及动员，启动，胞吐作用和亲吻和运行的机制。基于实验数据，我们认为单个β细胞在不同的葡萄糖浓度下激活。该模型再现了大部分的数据，它是非常好的测试，因此可以作为一个通用的模型，葡萄糖刺激的胰岛素分泌。模拟预测，吻和运行的胞吐事件的频率增加的影响是在不改变定性模式的情况下减少胰岛素分泌。我们的模型似乎也是第一个基于生理学的模型，重现了阶梯实验，该实验是“导数控制”的基础，即胰腺测量葡萄糖浓度变化率的能力。
When glucose is raised from a basal to stimulating level, the pancreatic islets respond with a typical biphasic insulin secretion pattern. Moreover, the pancreas is able to recognize the rate of change of the glucose concentration. We present a relatively simple model of insulin secretion from pancreatic β-cells, yet founded on solid physiological grounds and capable of reproducing a series of secretion patterns from perfused pancreases as well as from stimulated islets. The model includes the notion of distinct pools of granules as well as mechanisms such as mobilization, priming, exocytosis and kiss-and-run. Based on experimental data, we suggest that the individual β-cells activate at different glucose concentrations. The model reproduces most of the data it was tested against very well, and can therefore serve as a general model of glucose-stimulated insulin secretion. Simulations predict that the effect of an increased frequency of kiss-and-run exocytotic events is a reduction in insulin secretion without modification of the qualitative pattern. Our model also appears to be the first physiology-based one to reproduce the staircase experiment, which underlies ‘derivative control’, i.e. the pancreatic capacity of measuring the rate of change of the glucose concentration.
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影响因子：
3.4
作者：
Bertram, Richard;Satin, Leslie S.;Sherman, Arthur
通讯作者：
Sherman, Arthur
DOI：
10.1152/ajpendo.00421.2006
发表时间：
2007-07-01
影响因子：
5.1
作者：
Cobelli, Claudio;Toffolo, Gianna Maria;Rizza, Robert
通讯作者：
Rizza, Robert
影响因子：
7.7
作者：
Gerich, JE
通讯作者：
Gerich, JE
影响因子：
5.5
作者：
Fridlyand, Leonid E.;Harbeck, Mark C.;Philipson, Louis H.
通讯作者：
Philipson, Louis H.
DOI：
10.1073/pnas.0405149101
发表时间：
2004-08-31
影响因子：
11.1
作者：
Rocheleau, JV;Walker, GM;Piston, DW
通讯作者：
Piston, DW