PMID- 21829168
OWN - NLM
STAT- MEDLINE
DCOM- 20111031
LR  - 20230516
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 30
IP  - 18
DP  - 2011 Aug 9
TI  - Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal 
      balance in mice.
PG  - 3754-65
LID - 10.1038/emboj.2011.277 [doi]
AB  - It is well known that insulin can activate both PI3K/Akt pathway, which is 
      responsible for glucose uptake, and MAPK pathway, which is crucial for insulin 
      resistance formation. But, it is unclear exactly how the two pathways coordinate 
      to regulate insulin sensitivity upon hyperinsulinism stress of type 2 diabetes 
      mellitus (T2DM). Here, we show that an early response transcription factor Egr-1 
      could tilt the signalling balance by blocking PI3K/Akt signalling through PTEN 
      and augmenting Erk/MAPK signalling through GGPPS, resulting in insulin resistance 
      in adipocytes. Egr-1, PTEN and GGPPS are upregulated in the fat tissue of T2DM 
      patients and db/db mice. Egr-1 overexpression in epididymal fat induced 
      systematic insulin resistance in wild-type mice, and loss of Egr-1 function 
      improved whole-body insulin sensitivity in diabetic mice, which is mediated by 
      Egr-1 controlled PI3K/Akt and Erk/MAPK signalling balance. Therefore, we have 
      revealed, for the first time, the mechanism by which Egr-1 induces insulin 
      resistance under hyperinsulinism stress, which provides an ideal pharmacological 
      target since inhibiting Egr-1 can simultaneously block MAPK and augment PI3K/Akt 
      activation during insulin stimulation.
FAU - Yu, Xiao
AU  - Yu X
AD  - MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research 
      Center, Nanjing, China.
FAU - Shen, Ning
AU  - Shen N
FAU - Zhang, Ming-Liang
AU  - Zhang ML
FAU - Pan, Fei-Yan
AU  - Pan FY
FAU - Wang, Chen
AU  - Wang C
FAU - Jia, Wei-Ping
AU  - Jia WP
FAU - Liu, Chang
AU  - Liu C
FAU - Gao, Qian
AU  - Gao Q
FAU - Gao, Xiang
AU  - Gao X
FAU - Xue, Bin
AU  - Xue B
FAU - Li, Chao-Jun
AU  - Li CJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110809
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (Ggps1 protein, mouse)
RN  - 0 (Insulin)
RN  - 0 (Multienzyme Complexes)
RN  - EC 2.5.1.29 (Farnesyltranstransferase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Animals
MH  - Cell Line
MH  - Early Growth Response Protein 1/*metabolism
MH  - Farnesyltranstransferase/*metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Multienzyme Complexes/*metabolism
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Signal Transduction
PMC - PMC3173797
COIS- The authors declare that they have no conflict of interest.
EDAT- 2011/08/11 06:00
MHDA- 2011/11/01 06:00
PMCR- 2012/09/14
CRDT- 2011/08/11 06:00
PHST- 2010/12/20 00:00 [received]
PHST- 2011/06/29 00:00 [accepted]
PHST- 2011/08/11 06:00 [entrez]
PHST- 2011/08/11 06:00 [pubmed]
PHST- 2011/11/01 06:00 [medline]
PHST- 2012/09/14 00:00 [pmc-release]
AID - emboj2011277 [pii]
AID - 10.1038/emboj.2011.277 [doi]
PST - epublish
SO  - EMBO J. 2011 Aug 9;30(18):3754-65. doi: 10.1038/emboj.2011.277.