Department of Engineering, University Campus Bio-Medico of Rome, Via Á. del Portillo 21, 00128 Rome, Italy.
Department of Engineering, University Campus Bio-Medico of Rome, Via Á. del Portillo 21, 00128 Rome, Italy.
Biophys Chem. 2019 Nov;254:106247. doi: 10.1016/j.bpc.2019.106247. Epub 2019 Aug 9.
The β-cells dynamics is the regulator of insulin secretion in the pancreas, and its investigation is a central aspect in designing effective treatment strategies for diabetes. Despite great efforts, much is still unknown about the complex organization of such endocrine cells and realistic mathematical modeling represents a useful tool to elucidate key aspects of glucose control in humans. In this contribution, we study the human β-cells collective behaviour, by modeling their electric and metabolic coupling in a cluster, of size and architecture similar to human islets of Langerhans. We focus on the effect of coupling on various dynamics regimes observed in the islets, that are spiking and bursting on multiple timescales. In particular, we test the effect of hubs, that are highly glucose-sensitive β-cells, on the overall network dynamics, observing different modulation depending on the timescale of the dynamics. By properly taking into account the role of cells heterogeneity, recently emerged, our model effectively describes the effect of hubs on the synchronization of the islet response and the correlation of β-cells activity.
β 细胞动力学是胰腺中胰岛素分泌的调节剂，其研究是设计糖尿病有效治疗策略的核心方面。尽管付出了巨大努力，但对于这种内分泌细胞的复杂组织仍然知之甚少，而现实的数学建模代表了阐明人类葡萄糖控制关键方面的有用工具。在本研究中，我们通过模拟类似人类胰岛的簇中β 细胞的电和代谢偶联，研究了人类β 细胞的集体行为。我们专注于偶联对胰岛中观察到的各种动力学状态的影响，这些状态具有多个时间尺度的尖峰和爆发。特别是，我们测试了枢纽细胞（对葡萄糖高度敏感的β 细胞）对整体网络动力学的影响，观察到不同的调制取决于动力学的时间尺度。通过适当考虑最近出现的细胞异质性的作用，我们的模型有效地描述了枢纽细胞对胰岛反应同步和β 细胞活动相关性的影响。
