Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
EMBO J. 2011 Mar 2;30(5):835-45. doi: 10.1038/emboj.2010.361. Epub 2011 Feb 1.
MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated β-cells remain unclear. Here, we show that miRNA inactivation in β-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient β-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured β-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors.
微小 RNA（miRNAs）在胰腺发育中具有重要作用，但它们在分化的β细胞中的作用尚不清楚。在这里，我们显示成年小鼠β细胞中的 miRNA 失活会导致明显的糖尿病表型。尽管胰岛结构完整且分化标志物得以维持，但 Dicer1 缺陷的β细胞中胰岛素含量和胰岛素 mRNA 显著下降。由于胰岛素含量的变化，动物变得糖尿病。我们提供了一组 miRNA 参与调节胰岛素合成的证据。在培养的β细胞或分离的原代胰岛中特异性敲低 miR-24、miR-26、miR-182 或 miR-148 会下调胰岛素启动子活性和胰岛素 mRNA 水平。此外，miRNA 对胰岛素表达的调节与转录抑制因子（包括 Bhlhe22 和 Sox6）的上调有关。因此，成年胰腺中的 miRNAs 构成了一个新的网络，通过降低胰岛素转录抑制因子的表达来增强胰岛素的表达。
