Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
Front Endocrinol (Lausanne). 2022 Oct 21;13:1042611. doi: 10.3389/fendo.2022.1042611. eCollection 2022.
Diabetes is an epidemic with increasing incidence across the world. Most individuals who are afflicted by this disease have type 2 diabetes, but there are many who suffer from type 1, an autoimmune disorder. Both types of diabetes have complex genetic underpinnings that are further complicated by epigenetic and environmental factors. A less prevalent and often under diagnosed subset of diabetes cases are characterized by single genetic mutations and include Maturity Onset Diabetes of the Young (MODY) and Neonatal Diabetes Mellitus (NDM). While the mode of action and courses of treatment for all forms of diabetes are distinct, the diseases all eventually result in the dysfunction and/or death of the pancreatic β cell - the body's source of insulin. With loss of β cell function, blood glucose homeostasis is disrupted, and life-threatening complications arise. In this review, we focus on how model systems provide substantial insights into understanding β cell biology to inform our understanding of all forms of diabetes. The strengths and weaknesses of animal, hPSC derived β-like cell, and organoid models are considered along with discussion of GATA6, a critical transcription factor frequently implicated in pancreatic dysfunction with developmental origins; experimental studies of GATA6 have highlighted the advantages and disadvantages of how each of these model systems can be used to inform our understanding of β cell specification and function in health and disease.
糖尿病是一种在全球范围内发病率不断上升的流行病。大多数患有这种疾病的人患有 2 型糖尿病，但也有许多人患有 1 型糖尿病，这是一种自身免疫性疾病。这两种类型的糖尿病都有复杂的遗传基础，进一步受到表观遗传和环境因素的影响。糖尿病的一个不太常见且经常被诊断漏诊的亚组是由单一基因突变引起的，包括青少年发病的成年型糖尿病（MODY）和新生儿糖尿病（NDM）。虽然所有形式的糖尿病的作用模式和治疗过程都不同，但所有疾病最终都会导致胰腺 β 细胞的功能障碍和/或死亡——β 细胞是人体胰岛素的来源。随着 β 细胞功能的丧失，血糖稳态被打乱，出现危及生命的并发症。在这篇综述中，我们重点介绍了模型系统如何为理解 β 细胞生物学提供重要的见解，从而帮助我们理解所有形式的糖尿病。考虑了动物、hPSC 衍生的β样细胞和类器官模型的优缺点，并讨论了 GATA6，这是一种与发育起源相关的胰腺功能障碍频繁相关的关键转录因子；对 GATA6 的实验研究强调了这些模型系统中的每一个如何被用于了解健康和疾病中 β 细胞的特化和功能的优势和劣势。
