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 insulin are found in coronary heart disease and chronic heart failure. Although several studies have shown that insulin can stimulate ET-1 release from endothelial cell cultures, in vivo studies have yielded equivocal results. We sought to determine whether endogenous insulin at physiological concentrations leads to alterations in venous plasma ET-1 levels in healthy subjects. In addition, we investigated the effects of physiological and supraphysiological doses of insulin on the release of ET-1 from human umbilical vein endothelial cells (HUVECs) in vitro. In the in vitro experiment, ET-1 and insulin levels were measured during 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 mumol/L) for 4 hours before measurement of secreted ET-1. The in vivo study showed no significant alterations in venous plasma ET-1 levels during IVGTTs (maximum plasma insulin, 616.9 +/- 147.0 pmol/L [mean +/- SEM]). In the in vitro experiment, increases in ET-1 release were observed under serum-free conditions at 100 pmol/L (physiological) and 1 mumol/L (supraphysiological) insulin (ET-1, 22.4% and 46.4% higher than control cultures, respectively, both P < .05). Our results show that insulin at physiological concentrations does not alter plasma ET-1 levels in healthy individuals, but does stimulate its secretion from vascular endothelial cells in vitro. This may have implications for the study of elevated ET-1 in hyperinsulinemic states.