PMID- 20430890
OWN - NLM
STAT- MEDLINE
DCOM- 20100810
LR  - 20240318
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 285
IP  - 27
DP  - 2010 Jul 2
TI  - Paraquat-induced oxidative stress represses phosphatidylinositol 3-kinase 
      activities leading to impaired glucose uptake in 3T3-L1 adipocytes.
PG  - 20915-25
LID - 10.1074/jbc.M110.126482 [doi]
AB  - Accumulated evidence indicates that oxidative stress causes and/or promotes 
      insulin resistance; however, the mechanism by which this occurs is not fully 
      understood. This study was undertaken to elucidate the molecular mechanism by 
      which oxidative stress induced by paraquat impairs insulin-dependent glucose 
      uptake in 3T3-L1 adipocytes. We confirmed that paraquat-induced oxidative stress 
      decreased glucose transporter 4 (GLUT4) translocation to the cell surface, 
      resulting in repression of insulin-dependent 2-deoxyglucose uptake. Under these 
      conditions, oxidative stress did not affect insulin-dependent tyrosine 
      phosphorylation of insulin receptor, insulin receptor substrate (IRS)-1 and -2, 
      or binding of the phosphatidylinositol 3'-OH kinase (PI 3-kinase) p85 regulatory 
      subunit or p110alpha catalytic subunit to each IRS. In contrast, we found that 
      oxidative stress induced by paraquat inhibited activities of PI 3-kinase bound to 
      IRSs and also inhibited phosphorylation of Akt, the downstream serine/threonine 
      kinase that has been shown to play an essential role in insulin-dependent 
      translocation of GLUT4 to the plasma membrane. Overexpression of active form Akt 
      (myr-Akt) restored inhibition of insulin-dependent glucose uptake by paraquat, 
      indicating that paraquat-induced oxidative stress inhibits insulin signals 
      upstream of Akt. Paraquat treatment with and without insulin treatment decreased 
      the activity of class Ia PI 3-kinases p110alpha and p110beta that are mainly 
      expressed in 3T3-L1 adipocytes. However, paraquat treatment did not repress the 
      activity of the PI 3-kinase p110alpha mutated at Cys(90) in the p85 binding 
      region. These results indicate that the PI 3-kinase p110 is a possible primary 
      target of paraquat-induced oxidative stress to reduce the PI 3-kinase activity 
      and impaired glucose uptake in 3T3-L1 adipocytes.
FAU - Shibata, Michihiro
AU  - Shibata M
AD  - Department of Animal Sciences and Applied Biological Chemistry, Graduate School 
      of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113-8657, 
      Japan.
FAU - Hakuno, Fumihiko
AU  - Hakuno F
FAU - Yamanaka, Daisuke
AU  - Yamanaka D
FAU - Okajima, Hiroshi
AU  - Okajima H
FAU - Fukushima, Toshiaki
AU  - Fukushima T
FAU - Hasegawa, Takashi
AU  - Hasegawa T
FAU - Ogata, Tomomi
AU  - Ogata T
FAU - Toyoshima, Yuka
AU  - Toyoshima Y
FAU - Chida, Kazuhiro
AU  - Chida K
FAU - Kimura, Kumi
AU  - Kimura K
FAU - Sakoda, Hideyuki
AU  - Sakoda H
FAU - Takenaka, Asako
AU  - Takenaka A
FAU - Asano, Tomoichiro
AU  - Asano T
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100429
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (DNA Primers)
RN  - 0 (Glucose Transporter Type 4)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - PLG39H7695 (Paraquat)
SB  - IM
MH  - 3T3 Cells
MH  - Adenoviridae/genetics
MH  - Adipocytes/cytology/drug effects/*enzymology/metabolism
MH  - Animals
MH  - Biological Transport/*drug effects
MH  - Cell Line
MH  - Cell Membrane/metabolism
MH  - DNA Primers
MH  - Enzyme Repression
MH  - Glucose/*metabolism
MH  - Glucose Transporter Type 4/metabolism
MH  - Humans
MH  - Kidney
MH  - Mice
MH  - Oxidative Stress/*drug effects
MH  - Paraquat/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/biosynthesis/drug effects/*genetics
MH  - Plasmids
MH  - T-Lymphocytes/immunology
MH  - Transfection
PMC - PMC2898352
EDAT- 2010/05/01 06:00
MHDA- 2010/08/11 06:00
PMCR- 2011/07/02
CRDT- 2010/05/01 06:00
PHST- 2010/05/01 06:00 [entrez]
PHST- 2010/05/01 06:00 [pubmed]
PHST- 2010/08/11 06:00 [medline]
PHST- 2011/07/02 00:00 [pmc-release]
AID - S0021-9258(20)57379-1 [pii]
AID - M110.126482 [pii]
AID - 10.1074/jbc.M110.126482 [doi]
PST - ppublish
SO  - J Biol Chem. 2010 Jul 2;285(27):20915-25. doi: 10.1074/jbc.M110.126482. Epub 2010 
      Apr 29.