Not the second fiddle: α cell development, identity, and function in health and diabetes.
Not the second fiddle: α cell development, identity, and function in health and diabetes.
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DOI：
10.1530/joe-22-0297
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发表时间：
2023-08-01
影响因子：
4
通讯作者：
Sussel, Lori
中科院分区：
文献类型：
--
作者：
Brooks, Elliott P.;Sussel, Lori
历史和新兴研究提供了糖尿病中胰腺α细胞功能和特性恶化的证据。越来越多的人类组织和更复杂的分子技术的可用性揭示了α细胞功能和身份如何在健康条件下保持以及它们如何在应对压力时变得功能失调的关键见解。这些研究揭示了糖尿病之前和期间胰高血糖素分泌受损、α细胞电生理学变化、α细胞质量变化、α细胞转录失调和α-至-β细胞转化的证据。在这篇综述中，我们概述了健康和疾病中α细胞身份的研究现状。模型生物和人类中的证据表明，除了β细胞功能障碍外，糖尿病还与α细胞特性的根本失调有关。重要的是，表观遗传学研究表明，α细胞在关键的细胞特异性和糖尿病失调基因上保留了更多的稳定和开放的染色质，支持α细胞固有的表观遗传可塑性使它们容易受到转录变化的影响，从而增强糖尿病中的身份和功能丧失。因此，进一步研究α细胞的特性和功能对于充分理解糖尿病至关重要，并支持表明α细胞可能代表糖尿病治疗新β细胞的替代来源的研究。
Historic and emerging studies provide evidence for the deterioration of pancreatic α cell function and identity in diabetes mellitus. Increased access to human tissue and the availability of more sophisticated molecular technologies have revealed key insights into how α cell function and identity are preserved in healthy conditions and how they become dysfunctional in response to stress. These studies have revealed evidence of impaired glucagon secretion, shifts in α cell electrophysiology, changes in α cell mass, dysregulation of α cell transcription and α-to-β cell conversion prior to and during diabetes. In this review we outline the current state of research on α cell identity in health and disease. Evidence in model organisms and humans suggests that in addition to β cell dysfunction, diabetes is associated with a fundamental dysregulation of α cell identity. Importantly, epigenetic studies have revealed that α cells retain more poised and open chromatin at key cell-specific and diabetes-dysregulated genes, supporting the model that inherent epigenetic plasticity of α cells makes them susceptible to the transcriptional changes that potentiate the loss of identity and function seen in diabetes. Thus, further research into the maintenance of α cell identity and function is critical to fully understanding diabetes and support studies that suggest α cells could represent an alternative source of new β cells for diabetes treatment.
影响因子：
2.7
作者：
Mastracci TL;Wilcox CL;Arnes L;Panea C;Golden JA;May CL;Sussel L
通讯作者：
Sussel L