Functional implications of long non-coding RNAs in the pancreatic islets of Langerhans.
Functional implications of long non-coding RNAs in the pancreatic islets of Langerhans.
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DOI：
10.3389/fgene.2014.00209
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发表时间：
2014
影响因子：
3.7
通讯作者：
Eliasson L
中科院分区：
文献类型：
--
作者：
Esguerra JL;Eliasson L
2型糖尿病（T2 D）是一种复杂的疾病，其特征在于靶组织中的胰岛素抵抗和胰腺β细胞的胰岛素释放受损。作为葡萄糖稳态的中心组织，胰岛仍然是理解疾病的病理生理学的重要研究焦点。对人类胰岛的获取增加了对胰岛功能的了解，并且与RNA测序和相关技术的进步一起，揭示了人类胰岛细胞的转录和表观遗传景观。发现了数千个在胰岛中高度富集和/或在β细胞中特异性表达的长非编码RNA（lncRNA）转录物，指出了许多迄今未知的控制胰岛细胞功能的机制原理的另一层基因调控。在这里，我们回顾了基本的胰岛生理学，并提出了lncRNA在胰岛发育和内分泌细胞功能的功能意义。我们还考虑到啮齿动物和人类胰岛在形态和功能方面的重要差异，并建议物种特异性lncRNA如何部分影响基因调控，以定义生物体的独特表型身份及其组成细胞的功能。灵长类特异性lncRNA的意义将在糖尿病研究的各个方面都具有深远意义，但最重要的是在识别和开发新靶点以改善胰岛细胞功能作为治疗T2 D的治疗方法方面。
Type-2 diabetes (T2D) is a complex disease characterized by insulin resistance in target tissues and impaired insulin release from pancreatic beta cells. As central tissue of glucose homeostasis, the pancreatic islet continues to be an important focus of research to understand the pathophysiology of the disease. The increased access to human pancreatic islets has resulted in improved knowledge of islet function, and together with advances in RNA sequencing and related technologies, revealed the transcriptional and epigenetic landscape of human islet cells. The discovery of thousands of long non-coding RNA (lncRNA) transcripts highly enriched in the pancreatic islet and/or specifically expressed in the beta-cells, points to yet another layer of gene regulation of many hitherto unknown mechanistic principles governing islet cell functions. Here we review fundamental islet physiology and propose functional implications of the lncRNAs in islet development and endocrine cell functions. We also take into account important differences between rodent and human islets in terms of morphology and function, and suggest how species-specific lncRNAs may partly influence gene regulation to define the unique phenotypic identity of an organism and the functions of its constituent cells. The implication of primate-specific lncRNAs will be far-reaching in all aspects of diabetes research, but most importantly in the identification and development of novel targets to improve pancreatic islet cell functions as a therapeutic approach to treat T2D.