长链非编码RNA NONRATT021972小干扰RNA通过AKT信号通路使2型糖尿病大鼠肝葡萄糖激酶功能障碍恢复正常。
LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats.
作者信息
Song Miaomiao, Zou Lifang, Peng Lichao, Liu Shuangmei, Wu Bing, Yi Zhihua, Gao Yun, Zhang Chunping, Xu Hong, Xu Yurong, Tang Mengxia, Wang Shouyu, Xue Yun, Jia Tianyu, Zhao Shanhong, Liang Shangdong, Li Guilin
机构信息
a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
b Department of Cell Biology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
出版信息
Endocr Res. 2017 Aug;42(3):180-190. doi: 10.1080/07435800.2017.1292522. Epub 2017 Mar 10.
UNLABELLED
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.
未标记
2型糖尿病（T2DM）患者肝脏中葡萄糖激酶（GK）的表达和活性降低，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。某些长链非编码RNA（lncRNA）功能异常与多种疾病有关。
目的
本研究通过AKT信号通路探讨lncRNA NONRATT021972小分子干扰RNA（siRNA）对T2DM大鼠肝脏GK功能障碍的影响。
方法
研究2型糖尿病大鼠肝脏以及在高糖和高脂培养基中培养的肝细胞。通过蛋白质印迹法或逆转录聚合酶链反应检测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，且该升高与血糖水平升高有关。NONRATT021972 siRNA可提高磷酸化AKT（p-AKT）水平、GK表达和肝糖原合成。该siRNA还可降低T2DM大鼠以及在含脂肪酸的高糖培养基中培养的肝细胞中磷酸化糖原合酶激酶-3β（p-GSK-3β）水平和高血糖。CatRAPID预测NONRATT021972与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。
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