Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations

J Clin Endocrinol Metab. 2002 Mar;87(3):1419-22. doi: 10.1210/jcem.87.3.8462.


We have recently demonstrated that an infusion of a low dose of insulin reduces the intranuclear NF-kappa B (a pro-inflammatory transcription factor) content in MNC while also reducing the plasma concentration of NF-kappa B dependent pro-inflammatory cytokines and adhesion molecules. We have now tested the effect of insulin on the pro-inflammatory transcription factor, early growth response-1 (Egr-1) and plasma concentration of tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1), two major proteins whose expression is modulated by Egr-1. Insulin was infused at the rate of 2 IU/h in 5% dextrose (100 mL/h) and KCI (8 mmol/h) for 4 h in the fasting state in ten obese subjects. Blood samples were obtained at 0, 2, 4 and 6 h. MNC were isolated and their total homogenates and nuclear fractions were prepared and Egr-1 was measured by electrophoretic mobility shift assay (EMSA). Plasma TF and PAI-1 were assayed by ELISA. There was a significant fall in Egr-1 at 2 (66 +/- 14% of basal level) and 4 h (47 +/- 17% of the basal level; P<0.01). PAI-1 levels (basal = 100%) decreased significantly after insulin infusion at 2 h (57 +/- 6.7% of the basal level) and at 4 h (58 +/- 8.3% of the basal level; P<0.001). Plasma TF levels (basal = 100%) decreased to 76 +/- 7.7% of the basal level at 2 h and to 85 +/- 10.4% of the basal level at 4 h (P<0.05). Thus, insulin reduces intranuclear Egr-1 and the expression of TF and PAI-1. These data provide further evidence that insulin has an anti-inflammatory effect including the inhibition of TF and PAI-1 expression. These effects suggest a potential beneficial effect of insulin in thrombin formation and fibrinolysis in atherothrombosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • DNA-Binding Proteins / antagonists & inhibitors*
  • Early Growth Response Protein 1
  • Humans
  • Immediate-Early Proteins*
  • Insulin / blood
  • Insulin / pharmacology*
  • Middle Aged
  • Monocytes / metabolism*
  • Osmolar Concentration
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Thromboplastin / antagonists & inhibitors*
  • Thromboplastin / metabolism
  • Transcription Factors / antagonists & inhibitors*


  • Blood Glucose
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • Insulin
  • Plasminogen Activator Inhibitor 1
  • Transcription Factors
  • Thromboplastin