Insulin inhibits intranuclear nuclear factor kappaB and stimulates IkappaB in mononuclear cells in obese subjects: evidence for an anti-inflammatory effect?

Abstract

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.

• Authors: P Dandona, A Aljada, P Mohanty, H Ghanim, W Hamouda, E Assian, S Ahmad
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 86 Issue 7 Pg. 3257-65 (Jul 2001) ISSN: 0021-972X [Print] United States
• PMID: 11443198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Blood Glucose
• Chemokine CCL2
• I-kappa B Proteins
• Insulin
• NF-kappa B
• Phosphoproteins
• Plasminogen Activator Inhibitor 1
• Reactive Oxygen Species
• Intercellular Adhesion Molecule-1
• NADPH Oxidases
• neutrophil cytosolic factor 1

Topics

• Adult
• Anti-Inflammatory Agents (pharmacology)
• Blood Glucose (analysis)
• Chemokine CCL2 (blood)
• Female
• Humans
• I-kappa B Proteins (blood)
• Insulin (blood, pharmacology)
• Intercellular Adhesion Molecule-1 (blood)
• Kinetics
• Leukocytes, Mononuclear (metabolism)
• Male
• Middle Aged
• NADPH Oxidases
• NF-kappa B (antagonists & inhibitors, blood)
• Obesity (blood)
• Phosphoproteins (blood)
• Plasminogen Activator Inhibitor 1 (blood)
• Reactive Oxygen Species (metabolism)