Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Compr Physiol. 2020 Jul 8;10(3):893-932. doi: 10.1002/cphy.c190032.
The discovery that most mammalian genome sequences are transcribed to ribonucleic acids (RNA) has revolutionized our understanding of the mechanisms governing key cellular processes and of the causes of human diseases, including diabetes mellitus. Pancreatic islet cells were found to contain thousands of noncoding RNAs (ncRNAs), including micro-RNAs (miRNAs), PIWI-associated RNAs, small nucleolar RNAs, tRNA-derived fragments, long non-coding RNAs, and circular RNAs. While the involvement of miRNAs in islet function and in the etiology of diabetes is now well documented, there is emerging evidence indicating that other classes of ncRNAs are also participating in different aspects of islet physiology. The aim of this article will be to provide a comprehensive and updated view of the studies carried out in human samples and rodent models over the past 15 years on the role of ncRNAs in the control of α- and β-cell development and function and to highlight the recent discoveries in the field. We not only describe the role of ncRNAs in the control of insulin and glucagon secretion but also address the contribution of these regulatory molecules in the proliferation and survival of islet cells under physiological and pathological conditions. It is now well established that most cells release part of their ncRNAs inside small extracellular vesicles, allowing the delivery of genetic material to neighboring or distantly located target cells. The role of these secreted RNAs in cell-to-cell communication between β-cells and other metabolic tissues as well as their potential use as diabetes biomarkers will be discussed. © 2020 American Physiological Society. Compr Physiol 10:893-932, 2020.
大多数哺乳动物基因组序列被转录为核糖核酸（RNA）的发现，彻底改变了我们对调控关键细胞过程的机制以及包括糖尿病在内的人类疾病病因的认识。人们发现胰岛细胞含有数千种非编码 RNA（ncRNA），包括 micro-RNAs（miRNAs）、PIWI 相关 RNA、小核仁 RNA、tRNA 衍生片段、长非编码 RNA 和环状 RNA。虽然 miRNA 参与胰岛功能和糖尿病的病因现在已有充分的文献记载，但有新的证据表明，其他类别的 ncRNA 也参与了胰岛生理学的不同方面。本文的目的将是提供一个全面和更新的观点，即在过去 15 年中，在人类样本和啮齿动物模型中进行的关于 ncRNA 在控制α-和β-细胞发育和功能中的作用的研究，并强调该领域的最新发现。我们不仅描述了 ncRNA 在控制胰岛素和胰高血糖素分泌中的作用，还探讨了这些调节分子在胰岛细胞的增殖和存活中的作用，无论在生理还是病理条件下。现在已经确定，大多数细胞将其部分 ncRNA 释放到小型细胞外囊泡中，从而允许遗传物质递送到邻近或远处的靶细胞。这些分泌的 RNA 在β细胞和其他代谢组织之间的细胞间通讯中的作用及其作为糖尿病生物标志物的潜在用途将进行讨论。美国生理学会综合生理学 10:893-932,2020。
