PMID- 8571133
OWN - NLM
STAT- MEDLINE
DCOM- 19960305
LR  - 20220318
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 271
IP  - 5249
DP  - 1996 Feb 2
TI  - IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in 
      TNF-alpha- and obesity-induced insulin resistance.
PG  - 665-8
AB  - Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of insulin 
      resistance in obesity and diabetes through its ability to decrease the tyrosine 
      kinase activity of the insulin receptor (IR). Treatment of cultured murine 
      adipocytes with TNF-alpha was shown to induce serine phosphorylation of insulin 
      receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR 
      tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous 
      IRS-1, were resistant to TNF-alpha-mediated inhibition of IR signaling, whereas 
      transfected 32D cells that express IRS-1 were very sensitive to this effect of 
      TNF-alpha. An inhibitory form of IRS-1 was observed in muscle and fat tissues 
      from obese rats. These results indicate that TNF-alpha induces insulin resistance 
      through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
FAU - Hotamisligil, G S
AU  - Hotamisligil GS
AD  - Department of Cellular and Molecular Biology, Dana-Farber Cancer Institute, 
      Boston, MA, USA.
FAU - Peraldi, P
AU  - Peraldi P
FAU - Budavari, A
AU  - Budavari A
FAU - Ellis, R
AU  - Ellis R
FAU - White, M F
AU  - White MF
FAU - Spiegelman, B M
AU  - Spiegelman BM
LA  - eng
GR  - DK 42539/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, mouse)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Phosphoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - Adipose Tissue/metabolism
MH  - Animals
MH  - Cells, Cultured
MH  - Insulin/pharmacology
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin Resistance/*physiology
MH  - Male
MH  - Mice
MH  - Muscle, Skeletal/metabolism
MH  - Obesity/*metabolism
MH  - Phosphoproteins/metabolism/*physiology
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Zucker
MH  - Receptor, Insulin/*antagonists & inhibitors/metabolism
MH  - Serine/metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1996/02/02 00:00
MHDA- 1996/02/02 00:01
CRDT- 1996/02/02 00:00
PHST- 1996/02/02 00:00 [pubmed]
PHST- 1996/02/02 00:01 [medline]
PHST- 1996/02/02 00:00 [entrez]
AID - 10.1126/science.271.5249.665 [doi]
PST - ppublish
SO  - Science. 1996 Feb 2;271(5249):665-8. doi: 10.1126/science.271.5249.665.