PMID- 28281841 OWN - NLM STAT- MEDLINE DCOM- 20180501 LR - 20180501 IS - 1532-4206 (Electronic) IS - 0743-5800 (Linking) VI - 42 IP - 3 DP - 2017 Aug TI - LncRNA NONRATT021972 siRNA normalized the dysfunction of hepatic glucokinase through AKT signaling in T2DM rats. PG - 180-190 LID - 10.1080/07435800.2017.1292522 [doi] AB - 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-3beta. 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 3beta 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-3beta (p-GSK-3beta) 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. FAU - Song, Miaomiao AU - Song M AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Zou, Lifang AU - Zou L AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Peng, Lichao AU - Peng L AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Liu, Shuangmei AU - Liu S AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Wu, Bing AU - Wu B AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Yi, Zhihua AU - Yi Z AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Gao, Yun AU - Gao Y AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Zhang, Chunping AU - Zhang C AD - b Department of Cell Biology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Xu, Hong AU - Xu H AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Xu, Yurong AU - Xu Y AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Tang, Mengxia AU - Tang M AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Wang, Shouyu AU - Wang S AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Xue, Yun AU - Xue Y AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Jia, Tianyu AU - Jia T AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Zhao, Shanhong AU - Zhao S AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Liang, Shangdong AU - Liang S AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. FAU - Li, Guilin AU - Li G AD - a Department of Physiology , Basic Medical College of Nanchang University , Nanchang , Jiangxi , People's Republic of China. LA - eng PT - Journal Article DEP - 20170310 PL - England TA - Endocr Res JT - Endocrine research JID - 8408548 RN - 0 (RNA, Long Noncoding) RN - 0 (RNA, Small Interfering) RN - 0 (long non-coding RNA NONRATT021972, rat) RN - EC 2.7.1.2 (Glucokinase) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) SB - IM MH - Animals MH - Diabetes Mellitus, Experimental/*metabolism MH - Diabetes Mellitus, Type 2/*metabolism MH - Glucokinase/*metabolism MH - Male MH - Proto-Oncogene Proteins c-akt/*metabolism MH - RNA, Long Noncoding/*metabolism MH - RNA, Small Interfering/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction/*physiology OTO - NOTNLM OT - AKT OT - Glucokinase OT - Type 2 diabetes OT - long noncoding RNA EDAT- 2017/03/11 06:00 MHDA- 2018/05/02 06:00 CRDT- 2017/03/11 06:00 PHST- 2017/03/11 06:00 [pubmed] PHST- 2018/05/02 06:00 [medline] PHST- 2017/03/11 06:00 [entrez] AID - 10.1080/07435800.2017.1292522 [doi] PST - ppublish SO - Endocr Res. 2017 Aug;42(3):180-190. doi: 10.1080/07435800.2017.1292522. Epub 2017 Mar 10.