PMID- 11912559
OWN - NLM
STAT- MEDLINE
DCOM- 20020508
LR  - 20221207
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 51
IP  - 4
DP  - 2002 Apr
TI  - Tumor necrosis factor-alpha inhibits insulin-induced increase in endothelial 
      nitric oxide synthase and reduces insulin receptor content and phosphorylation in 
      human aortic endothelial cells.
PG  - 487-91
AB  - Insulin exerts a vasodilatory effect through the release of nitric oxide (NO) 
      from the endothelium. We have recently demonstrated that insulin also inhibits 
      the expression of intracellular adhesion molecule-1 (ICAM-1) and monocyte 
      chemoattractant protein-1 (MCP-1), 2 major proinflammatory mediators, by human 
      aortic endothelial cells (HAEC) and the proinflammatory mediator, nuclear factor 
      (NF-kappa B), in the nucleus in parallel with an increase in endothelial nitric 
      oxide synthase (e-NOS) expression. The inhibition of ICAM-1 by insulin is NO 
      dependent. Because tumor necrosis factor-alpha (TNF-a ) is proinflammatory and 
      may thus inhibit the action of insulin at the endothelial cell level, we have now 
      investigated whether TNF-a affects (1) insulin receptor content; (2) insulin 
      receptor (IR) autophosphorylation induced by insulin, and (3) e-NOS expression by 
      the endothelial cells. TNF-alpha (1 to 5 ng/mL) caused e-NOS inhibition in a 
      dose-dependent fashion as measured by Western blotting. This inhibition was 
      reduced with insulin addition. TNF-alpha also inhibited tyrosine 
      autophosphorylation of the IR in HAEC induced by insulin and reduced IR 
      beta-subunit protein expression in HAEC. These effects of insulin and TNF-alpha 
      were independent of cell proliferation, as cell counts did not change with 
      insulin or TNF-alpha. Our data demonstrate that TNF-alpha may exert its effect by 
      inhibiting IR autophosphorylation in HAEC and also by reducing IR protein (IRP) 
      expression. Although the inhibition of IR autophosphorylation by TNF-alpha is 
      known to occur at the adipocyte level, the data on the inhibitory effect of 
      TNF-alpha on insulin-induced e-NOS expression and IRP contents are novel.
CI  - Copyright 2002, Elsevier Science (USA). All rights reserved.
FAU - Aljada, Ahmad
AU  - Aljada A
AD  - Division of Endocrinology, Diabetes, and Metabolism, State University of New York 
      at Buffalo, Buffalo, USA.
FAU - Ghanim, Husam
AU  - Ghanim H
FAU - Assian, Ezzat
AU  - Assian E
FAU - Dandona, Paresh
AU  - Dandona P
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (Insulin)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Adult
MH  - Aorta
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Child
MH  - Endothelium, Vascular/cytology/drug effects/*metabolism
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Male
MH  - Nitric Oxide Synthase/drug effects/*metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Phosphorylation
MH  - Receptor, Insulin/drug effects/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - White People
EDAT- 2002/03/26 10:00
MHDA- 2002/05/09 10:01
CRDT- 2002/03/26 10:00
PHST- 2002/03/26 10:00 [pubmed]
PHST- 2002/05/09 10:01 [medline]
PHST- 2002/03/26 10:00 [entrez]
AID - S0026049502196843 [pii]
AID - 10.1053/meta.2002.31339 [doi]
PST - ppublish
SO  - Metabolism. 2002 Apr;51(4):487-91. doi: 10.1053/meta.2002.31339.