PMID- 31309546
OWN - NLM
STAT- MEDLINE
DCOM- 20200617
LR  - 20200617
IS  - 1873-3468 (Electronic)
IS  - 0014-5793 (Linking)
VI  - 593
IP  - 21
DP  - 2019 Nov
TI  - Egr-1 transcriptionally activates protein phosphatase PTP1B to facilitate 
      hyperinsulinemia-induced insulin resistance in the liver in type 2 diabetes.
PG  - 3054-3063
LID - 10.1002/1873-3468.13537 [doi]
AB  - During the development of type 2 diabetes mellitus (T2DM), hyperinsulinemia is 
      the earliest symptom. It is believed that long-term high insulin stimulation 
      might facilitate insulin resistance in the liver, but the underlying mechanism 
      remains unknown. Herein, we report that hyperinsulinemia could induce persistent 
      early growth response gene-1 (Egr-1) activation in hepatocytes, which provides 
      negative feedback inhibition of insulin sensitivity by inducing the expression of 
      protein tyrosine phosphatase-1B (PTP1B). Deletion of Egr-1 in the liver 
      remarkably decreases glucose production, thus improving systemic glucose 
      tolerance and insulin sensitivity. Mechanistic analysis indicates that Egr-1 
      inhibits insulin receptor phosphorylation by directly activating PTP1B 
      transcription in the liver. Our results reveal the molecular mechanism by which 
      hyperinsulinemia accelerates insulin resistance in hepatocytes during the 
      progression of T2DM.
CI  - (c) 2019 Federation of European Biochemical Societies.
FAU - Wu, Jing
AU  - Wu J
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Tao, Weiwei
AU  - Tao W
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Bu, Dandan
AU  - Bu D
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Zhao, Yue
AU  - Zhao Y
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Zhang, Tongyu
AU  - Zhang T
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Chong, Danyang
AU  - Chong D
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Xue, Bin
AU  - Xue B
AD  - Core Laboratory, Sir Run Run Hospital, Nanjing Medical University, China.
FAU - Xing, Zheng
AU  - Xing Z
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
FAU - Li, Chaojun
AU  - Li C
AUID- ORCID: 0000-0001-9474-7321
AD  - Medical School of Nanjing University, China.
AD  - Model Animal Research Center, Nanjing University, China.
LA  - eng
GR  - 31601153/National Natural Science Foundation of China/International
GR  - 530046/National Natural Science Foundation of China/International
GR  - 91857109/National Natural Science Foundation of China/International
GR  - BK20160619/Nature Science Foundation of Jiangsu Province/International
GR  - 201801B054/the program A/B for Outstanding PhD candidate of Nanjing 
      University/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190802
PL  - England
TA  - FEBS Lett
JT  - FEBS letters
JID - 0155157
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (Insulin)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1)
RN  - EC 3.1.3.48 (Ptpn1 protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Diabetes Mellitus, Type 2/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Early Growth Response Protein 1/*genetics/*metabolism
MH  - Gene Knockout Techniques
MH  - Glucose/metabolism
MH  - Glycogen/metabolism
MH  - Hyperinsulinism/*genetics/metabolism
MH  - Insulin/metabolism
MH  - Insulin Resistance
MH  - Liver/cytology/*metabolism
MH  - Male
MH  - Mice
MH  - Phosphorylation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 1/*genetics
MH  - Receptor, Insulin/metabolism
MH  - Transcriptional Activation
OTO - NOTNLM
OT  - PTP1B
OT  - Egr-1
OT  - hyperinsulinemia
OT  - insulin resistance
OT  - insulin signaling
OT  - liver
EDAT- 2019/07/17 06:00
MHDA- 2020/06/18 06:00
CRDT- 2019/07/17 06:00
PHST- 2019/05/09 00:00 [received]
PHST- 2019/06/26 00:00 [revised]
PHST- 2019/07/04 00:00 [accepted]
PHST- 2019/07/17 06:00 [pubmed]
PHST- 2020/06/18 06:00 [medline]
PHST- 2019/07/17 06:00 [entrez]
AID - 10.1002/1873-3468.13537 [doi]
PST - ppublish
SO  - FEBS Lett. 2019 Nov;593(21):3054-3063. doi: 10.1002/1873-3468.13537. Epub 2019 
      Aug 2.