title: LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Song
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zou
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Peng
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Shuangmei
authors.initials: S
authors.lastname: Liu
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yi
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.affiliation: b Department of Cell Biology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Zhang
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Mengxia
authors.initials: M
authors.lastname: Tang
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xue
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Tianyu
authors.initials: T
authors.lastname: Jia
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Shanhong
authors.initials: S
authors.lastname: Zhao
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Shangdong
authors.initials: S
authors.lastname: Liang
authors.affiliation: a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China.
authors.forename: Guilin
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005941:Glucokinase / Q000378:metabolism*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; C000611529:long non-coding RNA NONRATT021972, rat; D005941:Glucokinase; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; Glucokinase; Type 2 diabetes; long noncoding RNA