Miranda Mario A, Macias-Velasco Juan F, Lawson Heather A
Department of Genetics, Washington University School of Medicine, Saint Louis, Missouri.
Am J Physiol Endocrinol Metab. 2021 Apr 1;320(4):E716-E731. doi: 10.1152/ajpendo.00649.2020. Epub 2021 Feb 15.
Pancreatic β-cells perform glucose-stimulated insulin secretion, a process at the center of type 2 diabetes etiology. Efforts to understand how β-cells behave in healthy and stressful conditions have revealed a wide degree of morphological, functional, and transcriptional heterogeneity. Sources of heterogeneity include β-cell topography, developmental origin, maturation state, and stress response. Advances in sequencing and imaging technologies have led to the identification of β-cell subtypes, which play distinct roles in the islet niche. This review examines β-cell heterogeneity from morphological, functional, and transcriptional perspectives, and considers the relevance of topography, maturation, development, and stress response. It also discusses how these factors have been used to identify β-cell subtypes, and how heterogeneity is impacted by diabetes. We examine open questions in the field and discuss recent technological innovations that could advance understanding of β-cell heterogeneity in health and disease.
胰腺β细胞执行葡萄糖刺激的胰岛素分泌，这一过程是2型糖尿病病因的核心。为了解β细胞在健康和应激条件下的行为所做的努力揭示了广泛的形态、功能和转录异质性。异质性的来源包括β细胞的拓扑结构、发育起源、成熟状态和应激反应。测序和成像技术的进步已导致β细胞亚型的识别，这些亚型在胰岛微环境中发挥着不同的作用。本综述从形态、功能和转录角度审视β细胞异质性，并考虑拓扑结构、成熟、发育和应激反应的相关性。它还讨论了如何利用这些因素来识别β细胞亚型，以及异质性如何受到糖尿病的影响。我们审视了该领域的开放性问题，并讨论了可能推动对健康和疾病中β细胞异质性理解的最新技术创新。
