Dehghany Jaber, Hoboth Peter, Ivanova Anna, Mziaut Hassan, Müller Andreas, Kalaidzidis Yannis, Solimena Michele, Meyer-Hermann Michael
Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Paul Langerhans Institute Dresden of Helmholtz Centre Munich at University Clinic Carl Gustav Carus of TU Dresden and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
Traffic. 2015 Aug;16(8):797-813. doi: 10.1111/tra.12286. Epub 2015 May 1.
Insulin secretion from pancreatic β-cells in response to sudden glucose stimulation is biphasic. Prolonged secretion in vivo requires synthesis, delivery to the plasma membrane (PM) and exocytosis of insulin secretory granules (SGs). Here, we provide the first agent-based space-resolved model for SG dynamics in pancreatic β-cells. Using recent experimental data, we consider a single β-cell with identical SGs moving on a phenomenologically represented cytoskeleton network. A single exocytotic machinery mediates SG exocytosis on the PM. This novel model reproduces the measured spatial organization of SGs and insulin secretion patterns under different stimulation protocols. It proposes that the insulin potentiation effect and the rising second-phase secretion are mainly due to the increasing number of docking sites on the PM. Furthermore, it shows that 6 min after glucose stimulation, the 'newcomer' SGs are recruited from a region within less than 600 nm from the PM.
胰腺β细胞对突然的葡萄糖刺激产生的胰岛素分泌是双相的。体内的持续分泌需要胰岛素分泌颗粒（SGs）的合成、运输到质膜（PM）以及胞吐作用。在这里，我们提供了第一个基于主体的胰腺β细胞中SG动态的空间分辨模型。利用最近的实验数据，我们考虑一个具有相同SGs的单个β细胞在一个现象学表示的细胞骨架网络上移动。单个胞吐机制介导PM上的SG胞吐作用。这个新模型再现了不同刺激方案下测量到的SGs空间组织和胰岛素分泌模式。它提出胰岛素增强效应和上升的第二阶段分泌主要是由于PM上对接位点数量的增加。此外，它表明在葡萄糖刺激6分钟后，“新来者”SGs是从距离PM小于600纳米的区域招募的。
