Department of Bioengineering, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Nat Rev Endocrinol. 2022 Jan;18(1):9-22. doi: 10.1038/s41574-021-00568-0. Epub 2021 Oct 19.
Endocrine cells within the pancreatic islets of Langerhans are heterogeneous in terms of transcriptional profile, protein expression and the regulation of hormone release. Even though this heterogeneity has long been appreciated, only within the past 5 years have detailed molecular analyses led to an improved understanding of its basis. Although we are beginning to recognize why some subpopulations of endocrine cells are phenotypically different to others, arguably the most important consideration is how this heterogeneity affects the regulation of hormone release to control the homeostasis of glucose and other energy-rich nutrients. The focus of this Review is the description of how endocrine cell heterogeneity (and principally that of insulin-secreting β-cells) affects the regulation of hormone secretion within the islets of Langerhans. This discussion includes an overview of the functional characteristics of the different islet cell subpopulations and describes how they can communicate to influence islet function under basal and glucose-stimulated conditions. We further discuss how changes to the specific islet cell subpopulations or their numbers might underlie islet dysfunction in type 2 diabetes mellitus. We conclude with a discussion of several key open questions regarding the physiological role of islet cell heterogeneity.
胰岛内的内分泌细胞在转录谱、蛋白质表达和激素释放调节方面存在异质性。尽管这种异质性早已被人们所认识，但直到过去 5 年，详细的分子分析才使人们对其基础有了更好的理解。虽然我们开始认识到为什么一些内分泌细胞亚群在表型上与其他细胞不同，但可以说最重要的考虑因素是这种异质性如何影响激素释放的调节，以控制葡萄糖和其他富含能量的营养素的体内平衡。这篇综述的重点是描述内分泌细胞异质性（主要是胰岛素分泌β细胞）如何影响胰岛内激素分泌的调节。这一讨论包括对不同胰岛细胞亚群的功能特征的概述，并描述了它们如何在基础和葡萄糖刺激条件下进行通信以影响胰岛功能。我们进一步讨论了特定胰岛细胞亚群或其数量的变化如何导致 2 型糖尿病中胰岛功能障碍。最后，我们讨论了几个关于胰岛细胞异质性的生理作用的关键开放性问题。
