PMID- 11443198
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20220412
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 86
IP  - 7
DP  - 2001 Jul
TI  - Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in 
      mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?
PG  - 3257-65
AB  - In view of the fact that insulin resistance is associated with atherogenesis and 
      that troglitazone, an insulin sensitizer, has anti-inflammatory effects, which 
      may be potentially antiatherogenic in the long term, we have now investigated 
      whether insulin has potential anti-inflammatory effects. We infused 2.0 to 2.5 
      IU/h in 5% dextrose (100 mL/h) iv into 10 obese subjects for 4 h followed by 5% 
      dextrose alone for 2 h. The rate of insulin infusion was varied to maintain 
      glucose concentrations as close to the baseline as possible. Blood samples were 
      obtained before and at 2, 4, and 6 h. Subjects were also infused with 5% dextrose 
      without insulin and with saline on separate occasions. Intranuclear nuclear 
      factor kappaB (NFkappaB) in mononuclear cells fell at 2 and further at 4 h, 
      reverting toward the baseline at 6 h (P < 0.05). IkappaB increased significantly 
      at 2 h, increasing further at 4 h and remaining elevated at 6 h (P < 0.001). 
      Reactive oxygen species (ROS) generation by mononuclear cells fell significantly 
      at 2 h and fell further at 4 h; it partially reverted to baseline at 6 h (P < 
      0.005). p47(phox) subunit, the key protein of nicotinamide adenine dinucleotide 
      phosphate oxidase also fell at 2 h and 4 h, reverting toward the baseline at 6 h 
      (P < 0.05). In addition, soluble intercellular adhesion molecule-1 (sICAM-1), 
      monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 
      (PAI-1) fell significantly following insulin infusion. Glucose or saline 
      infusions without insulin caused no alteration in NFkappaB, IkappaB, ROS 
      generation, p47(phox) subunit, sICAM-1, MCP-1, or PAI-1. We conclude that insulin 
      has a potent acute anti-inflammatory effect including a reduction in intranuclear 
      NFkappaB, an increase in IkappaB, and decreases in ROS generation, p47(phox) 
      subunit, plasma soluble intercellular adhesion molecule-1 (sICAM-1), monocyte 
      chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1. 
      This acute anti-inflammatory effect, if demonstrated in the long term, may have 
      implications for atherosclerosis and its complications.
FAU - Dandona, P
AU  - Dandona P
AD  - Division of Endocrinology, Diabetes & Metabolism, State University of New York at 
      Buffalo and Kaleida Health, Buffalo, New York 14209, USA.
FAU - Aljada, A
AU  - Aljada A
FAU - Mohanty, P
AU  - Mohanty P
FAU - Ghanim, H
AU  - Ghanim H
FAU - Hamouda, W
AU  - Hamouda W
FAU - Assian, E
AU  - Assian E
FAU - Ahmad, S
AU  - Ahmad S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Blood Glucose)
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Insulin)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoproteins)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Reactive Oxygen Species)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.1 (neutrophil cytosolic factor 1)
SB  - IM
MH  - Adult
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Blood Glucose/analysis
MH  - Chemokine CCL2/blood
MH  - Female
MH  - Humans
MH  - I-kappa B Proteins/*blood
MH  - Insulin/blood/*pharmacology
MH  - Intercellular Adhesion Molecule-1/blood
MH  - Kinetics
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Male
MH  - Middle Aged
MH  - NADPH Oxidases
MH  - NF-kappa B/*antagonists & inhibitors/blood
MH  - Obesity/*blood
MH  - Phosphoproteins/blood
MH  - Plasminogen Activator Inhibitor 1/blood
MH  - Reactive Oxygen Species/metabolism
EDAT- 2001/07/10 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/07/10 10:00
PHST- 2001/07/10 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/07/10 10:00 [entrez]
AID - 10.1210/jcem.86.7.7623 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2001 Jul;86(7):3257-65. doi: 10.1210/jcem.86.7.7623.