许多研究探讨了长链非编码RNA XIST在糖尿病中的作用。本研究旨在通过微小RNA(miR)-181b-5p/N-myc下游调控基因2(NDRG2)轴来揭示XIST对妊娠期糖尿病(GDM)动物模型进展的调控机制。检测了GDM小鼠中XIST、miR-181b-5p和NDRG2的表达水平。对GDM小鼠进行增加和减少功能实验，检查葡萄糖代谢指标（空腹血糖（FBG）、空腹胰岛素（FINS）和胰岛素抵抗的家庭模型评估（HOMA-IR））、血清氧化应激因子（谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和丙二醛（MDA））、血清炎症因子（白细胞介素-1 β（IL-1β）、IL-6和肿瘤坏死因子α（TNF-α））、胰腺组织的病理变化和GDM小鼠胰岛的凋亡细胞。结果显示，GDM小鼠中XIST和NDRG2表达升高，而miR-181b-5p表达降低。下调XIST、NDRG2或上调miR-181b-5p可降低FBG水平、HOMA-IR，血清IL-1β、IL-6和TNF-α，以及MDA含量，增加FINS、GSH和SOD水平，减轻胰腺组织的病理变化，抑制GDM小鼠胰岛的凋亡细胞。沉默XIST通过调控miR-181b-5p/NDRG2轴减弱GDM小鼠的胰岛素抵抗。

Many studies have explored the role of lncRNA X inactivation-specific transcript (XIST) in diabetes. This study was designed to unravel the regulatory mechanism of XIST on animal models of gestational diabetes mellitus (GDM) progression via the microRNA (miR)-181b-5p/N-myc downstream-regulated gene 2 (NDRG2) axis. XIST, miR-181b-5p, and NDRG2 expression levels in GDM mice were detected. The GDM mice were subjected to gain- and loss-of-function assays to examine the change of glucose metabolism indices (fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR)), serum oxidative stress factors (glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA)), serum inflammatory factors (interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)), pathological changes of pancreatic tissues, and apoptotic cells in pancreatic islets in GDM mice. XIST and NDRG2 expression were elevated while miR-181b-5p expression was depleted in GDM mice. Down-regulated XIST or NDRG2 or up-regulated miR-181b-5p reduced the FBG level, HOMA-IR, and serum IL-1β, IL-6, and TNF-α, and MDA contents, elevated the FINS, GSH, and SOD level, mitigated pathological changes in pancreatic tissues, and decelerated apoptotic cells in pancreatic islets in GDM mice. Silenced XIST dampens insulin resistance in GDM mice via the modulation of the miR-181b-5p/NDRG2 axis.