Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function.
Transcriptional Regulation of the Pancreatic Islet: Implications for Islet Function.
复制标题
DOI：
10.1007/s11892-015-0635-0
复制
发表时间：
2015-09
影响因子：
4.2
通讯作者：
Ucar D
中科院分区：
文献类型：
--
作者：
Stitzel ML;Kycia I;Kursawe R;Ucar D
胰岛含有多个控制葡萄糖稳态的产生胰岛素的内分泌细胞。转录建立并维持胰岛细胞的命运和身份。胰岛转录的遗传和环境破坏触发细胞功能障碍和疾病。早期对特定胰岛基因（包括胰岛素（INS）和转录因子PDX 1）的转录调控研究，确定了第一个控制胰岛功能的顺式调控DNA序列和反式作用因子。在这里，我们回顾了人类胰岛“组学”研究如何重塑我们对胰岛（dys）功能和糖尿病转录调控的理解。首先，我们强调扩大胰岛转录本的数量，形式和功能和DNA转录调控元件控制其生产。接下来，我们将介绍遗传和环境扰动对胰岛转录的影响。最后，我们讨论了这些研究的新见解如何使我们的糖尿病研究界能够建立对糖尿病病理生理学的机械理解，并为临床医生提供量身定制的精确药物选择，以预防和治疗胰岛功能障碍和糖尿病。
Islets of Langerhans contain multiple hormone-producing endocrine cells controlling glucose homeostasis. Transcription establishes and maintains islet cellular fates and identities. Genetic and environmental disruption of islet transcription triggers cellular dysfunction and disease. Early transcriptional regulation studies of specific islet genes, including insulin (INS) and the transcription factor PDX1, identified the first cis-regulatory DNA sequences and trans-acting factors governing islet function. Here, we review how human islet “omics” studies are reshaping our understanding of transcriptional regulation in islet (dys)function and diabetes. First, we highlight the expansion of islet transcript number, form, and function and of DNA transcriptional regulatory elements controlling their production. Next, we cover islet transcriptional effects of genetic and environmental perturbation. Finally, we discuss how these studies’ emerging insights should empower our diabetes research community to build mechanistic understanding of diabetes pathophysiology and to equip clinicians with tailored, precision medicine options to prevent and treat islet dysfunction and diabetes.