Nittala Aparna, Wang Xujing
Max McGee National Research Center for Juvenile Diabetes & Human and Molecular Genetics Center, Medical College of Wisconsin and Children's Research Institute of the Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA.
Theor Biol Med Model. 2008 Aug 3;5:17. doi: 10.1186/1742-4682-5-17.
Insulin, the principal regulating hormone of blood glucose, is released through the bursting of the pancreatic islets. Increasing evidence indicates the importance of islet morphostructure in its function, and the need of a quantitative investigation. Recently we have studied this problem from the perspective of islet bursting of insulin, utilizing a new 3D hexagonal closest packing (HCP) model of islet structure that we have developed. Quantitative non-linear dependence of islet function on its structure was found. In this study, we further investigate two key structural measures: the number of neighboring cells that each beta-cell is coupled to, nc, and the coupling strength, gc.
BETA-cell clusters of different sizes with number of beta-cells nbeta ranging from 1-343, nc from 0-12, and gc from 0-1000 pS, were simulated. Three functional measures of islet bursting characteristics--fraction of bursting beta-cells fb, synchronization index lambda, and bursting period Tb, were quantified. The results revealed a hyperbolic dependence on the combined effect of nc and gc. From this we propose to define a dimensionless cluster coupling index or CCI, as a composite measure for islet morphostructural integrity. We show that the robustness of islet oscillatory bursting depends on CCI, with all three functional measures fb, lambda and Tb increasing monotonically with CCI when it is small, and plateau around CCI = 1.
CCI is a good islet function predictor. It has the potential of linking islet structure and function, and providing insight to identify therapeutic targets for the preservation and restoration of islet beta-cell mass and function.
胰岛素是血糖的主要调节激素，通过胰岛的爆发性释放。越来越多的证据表明胰岛形态结构在其功能中的重要性，以及进行定量研究的必要性。最近我们从胰岛素胰岛爆发的角度研究了这个问题，利用我们开发的一种新的胰岛结构三维六方最密堆积（HCP）模型。发现了胰岛功能对其结构的定量非线性依赖性。在本研究中，我们进一步研究两个关键的结构指标：每个β细胞连接的相邻细胞数量nc和耦合强度gc。
模拟了不同大小的β细胞簇，β细胞数量nbeta范围为1 - 343，nc范围为0 - 12，gc范围为0 - 1000 pS。对胰岛爆发特征的三个功能指标——爆发性β细胞的比例fb、同步指数λ和爆发周期Tb进行了量化。结果揭示了对nc和gc综合效应的双曲线依赖性。由此我们提议定义一个无量纲的簇耦合指数或CCI，作为胰岛形态结构完整性的综合指标。我们表明胰岛振荡爆发的稳健性取决于CCI，当CCI较小时，所有三个功能指标fb、λ和Tb都随CCI单调增加，并在CCI = 1左右达到平稳。
CCI是一个良好的胰岛功能预测指标。它有潜力将胰岛结构与功能联系起来，并为识别用于保存和恢复胰岛β细胞质量及功能的治疗靶点提供见解。
