A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets.
A local glucose-and oxygen concentration-based insulin secretion model for pancreatic islets.
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DOI：
10.1186/1742-4682-8-20
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发表时间：
2011-06-21
影响因子：
--
通讯作者：
Buchwald P
中科院分区：
文献类型：
--
作者：
Buchwald P
由于胰岛素是葡萄糖稳态的主要调节剂，因此描述葡萄糖诱导的胰岛素分泌动力学的定量模型具有明显的兴趣。在这里，引入一个计算模型，重点不是生物体水平的浓度，但对局部，细胞水平的葡萄糖-胰岛素动力学的定量建模，通过将详细的空间分布的浓度内孤立的无血管胰岛的兴趣。所有的营养消耗和激素释放速率被假定为遵循希尔型S形依赖于当地的浓度。胰岛素分泌速率取决于葡萄糖浓度及其时间梯度，分别导致第二和第一相反应。由于缺氧也可能是无血管胰岛中的重要限制因素，因此通过合并和扩展我们先前的胰岛细胞耗氧模型，也建立了氧和细胞活力考虑因素。有限元法（FEM）框架是用来结合联合收割机反应速率与质量传输的对流和扩散以及流体力学。该模型进行了校准，从动态葡萄糖刺激的胰岛素释放（GSIR）灌注研究与孤立的胰岛的实验结果。仍需要进一步优化，但计算的胰岛素对输入葡萄糖浓度逐步增加的反应与表征葡萄糖和氧依赖性的现有实验胰岛素释放数据非常一致。该模型可以详细描述胰岛内胰岛素、葡萄糖和氧水平的空间分布。与最近的观察结果一致，建模还表明，较小的胰岛在移植和/或封装时表现更好。胰岛素分泌模型通过将局部消耗和释放速率耦合到所有感兴趣物种的空间分布的计算来实现。所得到的葡萄糖-胰岛素控制系统适合于S形比例-积分-微分控制器的一般框架，广义PID控制器，更适合于生物系统，由于最大响应有限，生物系统总是非线性的。由于实现的一般框架，可以对任意几何形状进行模拟，包括培养的、灌注的、移植的和封装的胰岛。
Because insulin is the main regulator of glucose homeostasis, quantitative models describing the dynamics of glucose-induced insulin secretion are of obvious interest. Here, a computational model is introduced that focuses not on organism-level concentrations, but on the quantitative modeling of local, cellular-level glucose-insulin dynamics by incorporating the detailed spatial distribution of the concentrations of interest within isolated avascular pancreatic islets. All nutrient consumption and hormone release rates were assumed to follow Hill-type sigmoid dependences on local concentrations. Insulin secretion rates depend on both the glucose concentration and its time-gradient, resulting in second-and first-phase responses, respectively. Since hypoxia may also be an important limiting factor in avascular islets, oxygen and cell viability considerations were also built in by incorporating and extending our previous islet cell oxygen consumption model. A finite element method (FEM) framework is used to combine reactive rates with mass transport by convection and diffusion as well as fluid-mechanics. The model was calibrated using experimental results from dynamic glucose-stimulated insulin release (GSIR) perifusion studies with isolated islets. Further optimization is still needed, but calculated insulin responses to stepwise increments in the incoming glucose concentration are in good agreement with existing experimental insulin release data characterizing glucose and oxygen dependence. The model makes possible the detailed description of the intraislet spatial distributions of insulin, glucose, and oxygen levels. In agreement with recent observations, modeling also suggests that smaller islets perform better when transplanted and/or encapsulated. An insulin secretion model was implemented by coupling local consumption and release rates to calculations of the spatial distributions of all species of interest. The resulting glucose-insulin control system fits in the general framework of a sigmoid proportional-integral-derivative controller, a generalized PID controller, more suitable for biological systems, which are always nonlinear due to the maximum response being limited. Because of the general framework of the implementation, simulations can be carried out for arbitrary geometries including cultured, perifused, transplanted, and encapsulated islets.
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影响因子：
--
作者：
Fridlyand LE;Philipson LH
通讯作者：
Philipson LH
影响因子：
7.4
作者：
Dishinger, John F.;Reid, Kendra R.;Kennedy, Robert T.
通讯作者：
Kennedy, Robert T.
影响因子：
3.3
作者：
Cabrera, Over;Jacques-Silva, M. Caroline;Caicedo, Alejandro
通讯作者：
Caicedo, Alejandro
影响因子：
8.2
作者：
de Vos, P;Smedema, I;de Haan, BJ
通讯作者：
de Haan, BJ
影响因子：
7.7
作者：
DIONNE, KE;COLTON, CK;YARMUSH, ML
通讯作者：
YARMUSH, ML