Abstract:
Long noncoding RNAs (lncRNAs) are strongly associated with glucose homeostasis, but their roles remain largely unknown. In this study, the potential role of lncRNA-Snhg3 in glucose metabolism was evaluated both in vitro and in vivo. Here, we found a positive relationship between Snhg3 and hepatic glycogenesis. Glucose tolerance improved in hepatocyte-specific Snhg3 knock-in (Snhg3-HKI) mice, while it worsened in hepatocyte-specific Snhg3 knockout (Snhg3-HKO) mice. Furthermore, hepatic glycogenesis had shown remarkable increase in Snhg3-HKI mice and reduction in Snhg3-HKO mice, respectively. Mechanistically, Snhg3 increased mRNA and protein expression levels of PPP1R3B through inducing chromatin remodeling and promoting the phosphorylation of protein kinase B. Collectively, these results suggested that lncRNA-Snhg3 plays a critical role in hepatic glycogenesis.
摘要:
长链非编码RNA(lncRNA)与葡萄糖稳态密切相关,但是他们的角色在很大程度上仍然未知。在这项研究中,在体外和体内评估了lncRNA-Snhg3在葡萄糖代谢中的潜在作用。这里,我们发现Snhg3与肝糖原形成呈正相关。肝细胞特异性Snhg3敲入(Snhg3-HKI)小鼠的葡萄糖耐量得到改善,而在肝细胞特异性Snhg3敲除(Snhg3-HKO)小鼠中恶化。此外,在Snhg3-HKI小鼠中,肝糖原显着增加,在Snhg3-HKO小鼠中减少,分别。机械上,Snhg3通过诱导染色质重塑和促进蛋白激酶B的磷酸化而增加PPP1R3B的mRNA和蛋白表达水平。这些结果表明,lncRNA-Snhg3在肝糖生成中起关键作用。