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

J Clin Endocrinol Metab. 2001 Jul;86(7):3257-65. doi: 10.1210/jcem.86.7.7623.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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