PHYSIOLOGICAL HYPERINSULINEMIA IS NOT ASSOCIATED WITH ALTERATIONS IN VENOUS PLASMA-LEVELS OF ENDOTHELIN-1 IN HEALTHY-INDIVIDUALS

Elevations in circulating levels of both endothelin-1 (ET-1) and insul in are found in coronary heart disease and chronic heart failure. Alth ough several studies have shown that insulin can stimulate ET-1 releas e from endothelial cell cultures, in vivo studies have yielded equivoc al results. We sought to determine whether endogenous insulin at physi ological concentrations leads to alterations in venous plasma ET-1 lev els in healthy subjects. In addition, we investigated the effects of p hysiological and supraphysiological doses of insulin on the release of ET-1 from human umbilical vein endothelial cells (HUVECs) in vitro. I n the in vitro experiment, ET-1 and insulin levels were measured durin g an intravenous glucose tolerance test (IVGTT) in 10 healthy subjects . In the in vitro experiment, HUVECs were incubated in the absence of serum and with different concentrations of insulin (25 pmol/L to 1 mu mol/L) for 4 hours before measurement of secreted ET-1. The in vivo st udy showed no significant alterations in venous plasma ET-1 levels dur ing IVGTTs (maximum plasma insulin, 616.9 +/- 147.0 pmol/L (mean +/- S EMI). In the in vitro experiment, increases in ET-1 release were obser ved under serum-free conditions at 100 pmol/L (physiological) and 1 pm ol/L (supraphysiological) insulin (ET-1, 22.4% and 46.4% higher than c ontrol cultures, respectively, both P < .05). Our results show that in sulin at physiological concentrations does not alter plasma ET-1 level s in healthy individuals, but does stimulate its secretion from vascul ar endothelial cells in vitro. This may have implications for the stud y of elevated ET-1 in hyperinsulinemic states. Copyright (C) 1997 by W .B. Saunders Company.