No Evidence for Short-Term Regulation of Plasminogen Activator Inhibitor Activity by Insulin in Man

In cross-sectional studies a positive correlation has been found between circulating insulin, triglycerides and plasminogen activator inhibitor (PAI-1) activity. To directly examine the effect of insulin on PAI-1 activity in vivo, we determined the response of PAI-1 activity in 17 normal subjects to acute hyperinsulinemia (serum free insulin 92 +/- 8 mU/l) during maintenance of normoglycemia (plasma glucose 5.1 +/- 0.1 mmol/l). In 12 matched control subjects PAI-1 activity was measured during infusion of saline (serum free insulin 3.6 +/- 0.3 mU/l, plasma glucose 5.2 +/- 0.1 mmol/l). Plasma PAI-1 activity decreased during the insulin infusion from 9.0 +/- 1.4 to 5.6 +/- 0.8 U/ml (p less than 0.01), and during saline infusion from 7.0 +/- 1.4 to 4.3 +/- 0.6 U/ml (p less than 0.05). Serum triglyceride concentrations decreased from 1.09 +/- 0.20 to 0.76 +/- 0.09 mmol/l (p less than 0.001) during hyperinsulinemia but remained unchanged during the saline infusion (1.04 +/- 0.11 vs. 1.02 +/- 0.12 mmol/l, NS). We conclude that insulin does not acutely change plasma PAI-1 activity, and that acute insulin-induced changes in serum triglycerides occur independently from those of PAI-1 activity.