LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats
LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats
复制标题
LncRNA NONRATT021972 siRNA 通过 AKT 信号传导使 T2DM 大鼠肝葡萄糖激酶功能障碍正常化
DOI：
10.1080/07435800.2017.1292522
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发表时间：
2017-01-01
影响因子：
2.1
通讯作者：
Li, Guilin
中科院分区：
文献类型：
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作者：
Song, Miaomiao;Zou, Lifang;Li, Guilin
摘要 2 型糖尿病 (T2DM) 中肝葡萄糖激酶 (GK) 表达和活性降低，糖原合酶激酶 3 (GSK-3) 抑制 GK 的合成。在肝细胞中，蛋白激酶 B (PKB/AKT) 信号通路的激活可增强 GK 表达并抑制 GSK-3β 的磷酸化。某些长非编码 RNA (lncRNA) 的功能障碍与多种疾病有关。目的：本研究探讨了 lncRNA NONRATT021972 小干扰 RNA (siRNA) 通过 AKT 信号传导对 T2DM 大鼠肝 GK 功能障碍的影响。方法：研究了 2 型糖尿病大鼠的肝脏和在高葡萄糖和高脂肪酸培养基中培养的肝细胞。通过Western blotting或RT-PCR检测AKT、GK和GSK 3β表达的变化。应用生物信息学技术(CatRAPID)鉴定NONRATT021972 RNA的靶点。结果：我们发现2型糖尿病大鼠肝脏中lncRNA NONRATT021972水平升高，并且这种升高与血糖水平升高相关。 NONRATT021972 siRNA 增强磷酸 AKT (p-AKT) 水平、GK 表达和肝糖原合成。该 siRNA 还降低了 T2DM 大鼠以及在含有脂肪酸的高葡萄糖培养基中培养的肝细胞中的磷酸糖原合酶激酶-3β (p-GSK-3β) 水平和高血糖。 CatRAPID预测NONRATT021972和p-AKT之间存在相互作用。结论：LncRNA NONRATT021972 siRNA 可能对 T2DM 具有有益作用。
ABSTRACT Hepatic glucokinase (GK) expression and activity are decreased in type 2 diabetes mellitus (T2DM), and glycogen synthase kinase-3 (GSK-3) inhibits the synthesis of GK. In hepatocytes, the activation of the protein kinase B (PKB/AKT) signaling pathway enhances GK expression and inhibits the phosphorylation of GSK-3β. The dysfunction of certain long noncoding RNAs (lncRNAs) has been associated with a variety of diseases. Aims: This study explored the effects of the lncRNA NONRATT021972 small interfering RNA (siRNA) on the dysfunction of hepatic GK through AKT signaling in T2DM rats. Methods: Livers from type 2 diabetic rats and hepatocytes cultured in high glucose and high fatty acid media were studied. The changes in expression of AKT, GK and GSK 3β were detected by western blotting or RT-PCR. The application of bioinformatics technology (CatRAPID) was used to identify the targets of NONRATT021972 RNA. Results: We found that lncRNA NONRATT021972 levels in the liver were increased in type 2 diabetic rats, and the increase was associated with an increase in the blood glucose levels. The NONRATT021972 siRNA enhanced phospho-AKT (p-AKT) levels, GK expression and hepatic glycogen synthesis. This siRNA also reduced phospho-glycogen synthase kinase-3β (p-GSK-3β) levels and hyperglycemia in T2DM rats, as well as in hepatocytes cultured in high glucose media with fatty acids. CatRAPID predicted that there was the interaction between NONRATT021972 and p-AKT. Conclusions: LncRNA NONRATT021972 siRNA may have beneficial effects on T2DM.