Taurine upregulated gene 1 (Tug1) is a novel lncRNA that participates in growth, and the abnormal expression of Tug1 related to mouse islet cell dysfunction. A recent study revealed that intrauterine growth retardation (IUGR) related to the pathogenesis of diabetes. Here, we aimed to explore the role and mechanism of Tug1 in IUGR‐mediated islet dysfunction. We observed that newborn IUGR mice had lower body and pancreas weight and smaller islets than newborn control mice. After IUGR mice were given a normal diet, they showed catch‐up growth and abnormal glucose tolerance; however, the pancreas/body weight ratio remained low. Blood glucose, serum insulin and related gene expression showed mild recovery after overexpression of Tug1 in IUGR mice. Furthermore, Tug1 was enriched in the nuclei of MIN6 cells. Using RIP and CHIP analyses we found that Tug1 could regulate Hes1 expression by binding to EZH2 to affect insulin synthesis in MIN6 cells. These findings indicate that lncRNA Tug1 could regulate the expression of Hes1 via EZH2‐driven H3K27 methylation and affect insulin production.

中文翻译：

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lncRNA Tug1在宫内发育迟缓小鼠模型中的胰岛功能障碍中的机制。

牛磺酸上调基因1（Tug1）是一种参与生长的新型lncRNA，Tug1的异常表达与小鼠胰岛细胞功能异常有关。最近的一项研究表明，宫内发育迟缓（IUGR）与糖尿病的发病机制有关。在这里，我们旨在探讨Tug1在IUGR介导的胰岛功能障碍中的作用和机制。我们观察到，新生IUGR小鼠的体重和胰脏重量比新生对照组的小鼠低，胰岛更小。给予IUGR小鼠正常饮食后，它们表现出追赶性生长和异常的葡萄糖耐量。然而，胰腺/体重比仍然很低。在IUGR小鼠中Tug1过表达后，血糖，血清胰岛素和相关基因表达显示出轻度恢复。此外，Tug1富含MIN6细胞的细胞核。使用RIP和CHIP分析，我们发现Tug1可以通过与EZH2结合来调节Hes1表达，从而影响MIN6细胞中的胰岛素合成。这些发现表明，lncRNA Tug1可以通过EZH2驱动的H3K27甲基化调节Hes1的表达，并影响胰岛素的产生。