CIRCULATING ENDOTHELIN-1 LEVELS INCREASE DURING EUGLYCEMIC HYPERINSULINEMIC CLAMP IN LEAN NIDDM MEN

OBJECTIVE- To evaluate whether or not insulin stimulates endothelin (E T)-1 secretion in vivo. RESEARCH DESIGN AND METHODS- Plasma ET-1 level s were evaluated in 16 lean normotensive men with non-insulin-dependen t diabetes mellitus (NIDDM) (mean age 50.3 +/- 4.1 years) during eithe r a 2-h euglycemic hyperinsulinemic clamp (40 mU insulin.m(-2).min(-1) ) or placebo infusion (50 mi isotonic saline) according to a single-bl ind randomized crossover protocol. RESULTS- Circulating ET-1 levels in creased during the euglycemic hyperinsulinemic clamp (from 0.88 +/- 0. 38 pg/ml at time 0 to 1.66 +/- 0.22 pg/ml and 1.89 +/- 0.99 pg/ml at 6 0 and 120 min, respectively [P < 0.05 vs. time 0]) and returned to bas eline levels after the discontinuation of insulin infusion (0.71 +/- 0 .22 pg/ml after a 30-min period of recovery [NS]). Compared with place bo, the euglycemic hyperinsulinemic clamp induced a significant increa se in plasma ET-1 levels at 60 min (P < 0.0001) and 120 min (P < 0.000 1). Changes in basal insulin levels and corresponding changes in circu lating ET-1 levels after a 2-h euglycemic hyperinsulinemic clamp were significantly correlated (r = 0.771, P < 0.0001). A possible unfavorab le effect of ET-1 on the tissue sensitivity to insulin-stimulated gluc ose uptake was suggested by the presence of a negative correlation bet ween total glucose uptake and baseline ET-1 levels (r = -0.498, P < 0. 05). CONCLUSIONS- Our findings indicate that circulating ET-1 levels s ignificantly increase during euglycemic hyperinsulinemic clamp in men with NIDDM. The negative correlation between total glucose uptake and circulating ET-1 levels suggests that the peptide might exert negative effects on the insulin sensitivity of target tissues. The consequent increase in insulin secretion as well as the insulin-related ET-1 rele ase from endothelial cells could favor the development of diabetes-rel ated vascular lesions.