PMID- 29577871
OWN - NLM
STAT- MEDLINE
DCOM- 20190205
LR  - 20220727
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 152
DP  - 2018 Jun
TI  - Long noncoding RNA MALAT1 regulates generation of reactive oxygen species and the 
      insulin responses in male mice.
PG  - 94-103
LID - S0006-2952(18)30124-2 [pii]
LID - 10.1016/j.bcp.2018.03.019 [doi]
AB  - The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long 
      noncoding RNA and its overexpression is associated with the development of many 
      types of malignancy. MALAT1 null mice show no overt phenotype. However, in 
      transcriptome analysis of MALAT1 null mice we found significant upregulation of 
      nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulated antioxidant 
      genes including Nqo1 and Cat with significant reduction in reactive oxygen 
      species (ROS) and greatly reduced ROS-generated protein carbonylation in 
      hepatocyte and islets. We performed lncRNA pulldown assay using biotinylated 
      antisense oligonucleotides against MALAT1 and found MALAT1 interacted with Nrf2, 
      suggesting Nrf2 is transcriptionally regulated by MALAT1. Exposure to excessive 
      ROS has been shown to cause insulin resistance through activation of c-Jun 
      N-terminal kinase (JNK) which leads to inhibition of insulin receptor substrate 1 
      (IRS-1) and insulin-induced phosphorylation of serine/threonine kinase Akt. We 
      found MALAT1 ablation suppressed JNK activity with concomitant insulin-induced 
      activation of IRS-1 and phosphorylation of Akt suggesting MALAT1 regulated 
      insulin responses. MALAT1 null mice exhibited sensitized insulin-signaling 
      response to fast-refeeding and glucose/insulin challenges and significantly 
      increased insulin secretion in response to glucose challenge in isolated MALAT1 
      null islets, suggesting an increased insulin sensitivity. In summary, we 
      demonstrate that MALAT1 plays an important role in regulating insulin sensitivity 
      and has the potential as a therapeutic target for the treatment of diabetes as 
      well as other diseases caused by excessive exposure to ROS.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Chen, Jingshu
AU  - Chen J
AD  - State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 
      China.
FAU - Ke, Sui
AU  - Ke S
AD  - Texas A&M University, United States.
FAU - Zhong, Lei
AU  - Zhong L
AD  - Hunan Agriculture University, Hunan, China.
FAU - Wu, Jing
AU  - Wu J
AD  - Hunan Agriculture University, Hunan, China.
FAU - Tseng, Alexander
AU  - Tseng A
AD  - Texas A&M University, United States.
FAU - Morpurgo, Benjamin
AU  - Morpurgo B
AD  - Texas A&M Institute for Genomic Medicine, United States.
FAU - Golovko, Andrei
AU  - Golovko A
AD  - Texas A&M Institute for Genomic Medicine, United States.
FAU - Wang, Gang
AU  - Wang G
AD  - Texas A&M University, United States.
FAU - Cai, James J
AU  - Cai JJ
AD  - Texas A&M University, United States.
FAU - Ma, Xi
AU  - Ma X
AD  - State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 
      China.
FAU - Li, Defa
AU  - Li D
AD  - State Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, 
      China.
FAU - Tian, Yanan
AU  - Tian Y
AD  - Department of Veterinary Physiology and Pharmacology, Texas A&M University, 
      College Station, TX, United States. Electronic address: ytian@cvm.tamu.edu.
LA  - eng
GR  - R01 ES009859/ES/NIEHS NIH HHS/United States
GR  - R13 ES028073/ES/NIEHS NIH HHS/United States
GR  - R21 AI152050/AI/NIAID NIH HHS/United States
GR  - P30 ES023512/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180322
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Insulin)
RN  - 0 (Malat1 long non-coding RNA, mouse)
RN  - 0 (RNA, Long Noncoding)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Animals
MH  - Gene Expression Regulation/drug effects
MH  - Insulin/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Oxidative Stress
MH  - Protein Carbonylation
MH  - RNA, Long Noncoding/genetics/*metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Insulin resistance
OT  - Long noncoding RNA
OT  - Oxidative stress
OT  - Reactive oxygen species
OT  - T2DM
EDAT- 2018/03/27 06:00
MHDA- 2019/02/06 06:00
CRDT- 2018/03/27 06:00
PHST- 2018/02/16 00:00 [received]
PHST- 2018/03/20 00:00 [accepted]
PHST- 2018/03/27 06:00 [pubmed]
PHST- 2019/02/06 06:00 [medline]
PHST- 2018/03/27 06:00 [entrez]
AID - S0006-2952(18)30124-2 [pii]
AID - 10.1016/j.bcp.2018.03.019 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2018 Jun;152:94-103. doi: 10.1016/j.bcp.2018.03.019. Epub 2018 
      Mar 22.