Exploring pancreatic beta-cell subgroups and their connectivity

IF 18.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Nature metabolism Pub Date : 2024-08-08 DOI:10.1038/s42255-024-01097-6
Guy A. Rutter, Anne Gresch, Luis Delgadillo Silva, Richard K. P. Benninger
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Abstract

Functional pancreatic islet beta cells are essential to ensure glucose homeostasis across species from zebrafish to humans. These cells show significant heterogeneity, and emerging studies have revealed that connectivity across a hierarchical network is required for normal insulin release. Here, we discuss current thinking and areas of debate around intra-islet connectivity, cellular hierarchies and potential “controlling” beta-cell populations. We focus on methodologies, including comparisons of different cell preparations as well as in vitro and in vivo approaches to imaging and controlling the activity of human and rodent islet preparations. We also discuss the analytical approaches that can be applied to live-cell data to identify and study critical subgroups of cells with a disproportionate role in control Ca2+ dynamics and thus insulin secretion (such as “first responders”, “leaders” and “hubs”, as defined by Ca2+ responses to glucose stimulation). Possible mechanisms by which this hierarchy is achieved, its physiological relevance and how its loss may contribute to islet failure in diabetes mellitus are also considered. A glossary of terms and links to computational resources are provided.

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探索胰腺β细胞亚群及其连接性
从斑马鱼到人类,功能性胰岛β细胞对确保葡萄糖平衡至关重要。这些细胞表现出明显的异质性,新的研究显示,正常的胰岛素释放需要一个分层网络的连接。在此,我们将讨论当前围绕胰岛内部连通性、细胞层次结构和潜在 "控制 "β细胞群的思路和争论领域。我们将重点放在方法论上,包括不同细胞制备的比较以及体外和体内成像和控制人类和啮齿动物胰岛制备活动的方法。我们还讨论了可应用于活细胞数据的分析方法,以识别和研究在控制 Ca2+ 动态从而控制胰岛素分泌方面起着不成比例作用的关键细胞亚群(如根据 Ca2+ 对葡萄糖刺激的反应定义的 "第一反应者"、"领导者 "和 "枢纽")。此外,还探讨了实现这种层次结构的可能机制、其生理相关性以及其缺失如何导致糖尿病患者的胰岛功能衰竭。本文提供了术语表和计算资源链接。
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来源期刊
Nature metabolism
Nature metabolism ENDOCRINOLOGY & METABOLISM-
CiteScore
27.50
自引率
2.40%
发文量
170
期刊介绍: Nature Metabolism is a peer-reviewed scientific journal that covers a broad range of topics in metabolism research. It aims to advance the understanding of metabolic and homeostatic processes at a cellular and physiological level. The journal publishes research from various fields, including fundamental cell biology, basic biomedical and translational research, and integrative physiology. It focuses on how cellular metabolism affects cellular function, the physiology and homeostasis of organs and tissues, and the regulation of organismal energy homeostasis. It also investigates the molecular pathophysiology of metabolic diseases such as diabetes and obesity, as well as their treatment. Nature Metabolism follows the standards of other Nature-branded journals, with a dedicated team of professional editors, rigorous peer-review process, high standards of copy-editing and production, swift publication, and editorial independence. The journal has a high impact factor, has a certain influence in the international area, and is deeply concerned and cited by the majority of scholars.
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