Multilevel synchronization of human β-cells networks.

Frontiers in network physiology Pub Date : 2023-09-22 eCollection Date: 2023-01-01 DOI:10.3389/fnetp.2023.1264395
Nicole Luchetti, Simonetta Filippi, Alessandro Loppini
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Abstract

β-cells within the endocrine pancreas are fundamental for glucose, lipid and protein homeostasis. Gap junctions between cells constitute the primary coupling mechanism through which cells synchronize their electrical and metabolic activities. This evidence is still only partially investigated through models and numerical simulations. In this contribution, we explore the effect of combined electrical and metabolic coupling in β-cell clusters using a detailed biophysical model. We add heterogeneity and stochasticity to realistically reproduce β-cell dynamics and study networks mimicking arrangements of β-cells within human pancreatic islets. Model simulations are performed over different couplings and heterogeneities, analyzing emerging synchronization at the membrane potential, calcium, and metabolites levels. To describe network synchronization, we use the formalism of multiplex networks and investigate functional network properties and multiplex synchronization motifs over the structural, electrical, and metabolic layers. Our results show that metabolic coupling can support slow wave propagation in human islets, that combined electrical and metabolic synchronization is realized in small aggregates, and that metabolic long-range correlation is more pronounced with respect to the electrical one.

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人类β细胞网络的多级同步。
胰腺内分泌中的β细胞是葡萄糖、脂质和蛋白质稳态的基础。细胞之间的间隙连接构成了主要的耦合机制,细胞通过该机制同步其电活动和代谢活动。这一证据仍然只是通过模型和数值模拟进行了部分研究。在这篇文章中,我们使用详细的生物物理模型探索了β细胞簇中电和代谢耦合的影响。我们增加了异质性和随机性,以真实地再现β细胞动力学,并研究模拟人类胰岛内β细胞排列的网络。在不同的耦合和非均质性上进行模型模拟,分析膜电位、钙和代谢物水平上出现的同步现象。为了描述网络同步,我们使用了多重网络的形式,并研究了结构、电学和代谢层上的功能网络特性和多重同步基序。我们的研究结果表明,代谢耦合可以支持人类胰岛中的慢波传播,在小聚集体中实现了电和代谢的联合同步,并且代谢的长程相关性相对于电的相关性更明显。
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