Department of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005, Lausanne, Switzerland.
Department of Clinical Sciences-Malmö, Lund University Diabetes Centre, Lund University, Clinical Research Centre, SUS, Malmö, Sweden.
Diabetologia. 2017 Oct;60(10):1977-1986. doi: 10.1007/s00125-017-4368-2. Epub 2017 Jul 16.
AIMS/HYPOTHESIS: P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) are small non-coding RNAs that interact with PIWI proteins and guide them to silence transposable elements. They are abundantly expressed in germline cells and play key roles in spermatogenesis. There is mounting evidence that piRNAs are also present in somatic cells, where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta cell activities.
piRNA profiling of rat pancreatic islets was performed by microarray analysis. The functions of piRNAs were investigated by silencing the two main Piwi genes or by modulating the level of selected piRNAs in islet cells.
We detected about 18,000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development. Moreover, we identified changes in the level of several piRNAs in the islets of Goto-Kakizaki rats, a well-established animal model of type 2 diabetes. Silencing of Piwil2 or Piwil4 genes in adult rat islets caused a reduction in the level of several piRNAs and resulted in defective insulin secretion and increased resistance of the cells to cytokine-induced cell death. Furthermore, overexpression in the islets of control animals of two piRNAs that are upregulated in diabetic rats led to a selective defect in glucose-induced insulin release.
CONCLUSIONS/INTERPRETATION: Our results provide evidence for a role of PIWI proteins and their associated piRNAs in the control of beta cell functions, and suggest a possible involvement in the development of type 2 diabetes.
Data have been deposited in Gene Expression Omnibus repository under the accession number GSE93792. Data can be accessed via the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ojklueugdzehpkv&acc=GSE93792.
目的/假设：P 元素诱导的 Wimpy 测试（PIWI）相互作用 RNA（piRNAs）是与 PIWI 蛋白相互作用并指导其沉默转座元件的小非编码 RNA。它们在生殖细胞中大量表达，在精子发生中发挥关键作用。越来越多的证据表明，piRNAs 也存在于体细胞中，在那里它们可能完成额外的调节任务。本研究的目的是鉴定在胰岛中表达的 piRNAs，并确定它们是否参与控制β细胞活性。
通过微阵列分析对大鼠胰岛的 piRNA 进行分析。通过沉默两个主要的 Piwi 基因或调节胰岛细胞中选定的 piRNA 水平来研究 piRNA 的功能。
我们在大鼠胰岛中检测到约 18000 个 piRNAs，其中许多在胰岛出生后发育过程中差异表达。此外，我们还发现 Goto-Kakizaki 大鼠胰岛中的几种 piRNA 水平发生变化，Goto-Kakizaki 大鼠是 2 型糖尿病的一种成熟动物模型。成年大鼠胰岛中 Piwil2 或 Piwil4 基因的沉默导致几种 piRNA 水平降低，并导致胰岛素分泌缺陷和细胞对细胞因子诱导的细胞死亡的抵抗力增加。此外，在对照组动物的胰岛中过表达两种在糖尿病大鼠中上调的 piRNA 会导致葡萄糖诱导的胰岛素释放选择性缺陷。
结论/解释：我们的研究结果为 PIWI 蛋白及其相关 piRNA 在控制β细胞功能中的作用提供了证据，并提示它们可能参与 2 型糖尿病的发生。
数据已在基因表达综合数据库中以 GSE93792 号存入。可以通过以下链接访问数据：https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ojklueugdzehpkv&acc=GSE93792。
