Insulin inhibits intranuclear nuclear factor kappa B and stimulates I kappa B in mononuclear cells in obese subjects: Evidence for an anti-inflammatory effect?

In view of the fact that insulin resistance is associated with atherogenesi s and that troglitazone, an insulin sensitizer, has anti-inflammatory effec ts, which may be potentially antiatherogenic in the long term, we have now investigated whether insulin has potential antiinflammatory effects. We inf used 2.0 to 2.5 IU/h in 5% dextrose (100 mL/h) iv into 10 obese subjects fo r 4 h followed by 5% dextrose alone for 2 h. The rate of insulin infusion w as varied to maintain glucose concentrations as close to the baseline as po ssible. Blood samples were obtained before and at 2, 4, and 6 h. Subjects w ere also infused with 5% dextrose without insulin and with saline on separa te occasions. Intranuclear nuclear factor kappaB (NF kappaB) in mononuclear cells fell at 2 and further at 4 h, reverting toward the baseline at 6 h ( P < 0.05). I kappaB 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) su bunit, the key protein of nicotinamide adenine dinucleotide phosphate oxida se 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), monocy te chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1) fell significantly following insulin infusion. Glucose or saline i nfusions without insulin caused no alteration in NF kappaB, I kappaB, ROS g eneration, p47(phox) subunit, sICAM-1, MCP-1, or PAI-1. We conclude that insulin has a potent acute anti-inflammatory effect includ ing a reduction in intranuclear NF kappaB, an increase in I kappaB, and dec reases in ROS generation, p47(phox) subunit, plasma soluble intercellular a dhesion molecule-1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), a nd plasminogen activator inhibitor-1 (PAI-1). This acute anti-inflammatory effect, if demonstrated in the long term, may have implications for atheros clerosis and its complications.