Circulating endothelin-1 levels increase during euglycemic hyperinsulinemic clamp in lean NIDDM men.
OBJECTIVE
To evaluate whether or not insulin stimulates endothelin (ET)-1 secretion in vivo.


METHODS
Plasma ET-1 levels were evaluated in 16 lean normotensive men with non-insulin-dependent diabetes mellitus (NIDDM) (mean age 50.3 +/- 4.1 years) during either a 2-h euglycemic hyperinsulinemic clamp (40 mU insulin.m-2.min-1) or placebo infusion (50 ml isotonic saline) according to a single-blind randomized crossover protocol.


RESULTS
Circulating ET-1 levels increased 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 60 and 120 min, respectively [P < 0.05 vs. time 0]) and returned to baseline levels after the discontinuation of insulin infusion (0.71 +/- 0.22 pg/ml after a 30-min period of recovery [NS]). Compared with placebo, the euglycemic hyperinsulinemic clamp induced a significant increase in plasma ET-1 levels at 60 min (P < 0.0001) and 120 min (P < 0.0001). Changes in basal insulin levels and corresponding changes in circulating ET-1 levels after a 2-h euglycemic hyperinsulinemic clamp were significantly correlated (r = 0.771, P < 0.0001). A possible unfavorable effect of ET-1 on the tissue sensitivity to insulin-stimulated glucose uptake was suggested by the presence of a negative correlation between total glucose uptake and baseline ET-1 levels (r = -0.498, P < 0.05).


CONCLUSIONS
Our findings indicate that circulating ET-1 levels significantly 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 release from endothelial cells could favor the development of diabetes-related vascular lesions.
Ferri
C
C
Istituto di I Clinica Medica, Università La Sapienza, Rome, Italy.
Carlomagno
A
A
Coassin
S
S
Baldoncini
R
R
Cassone Faldetta
M R
MR
Laurenti
O
O
Properzi
G
G
Santucci
A
A
De Mattia
G
G
D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D016232:Endothelins / Q000097:blood* / Q000378:metabolism; D015309:Glucose Clamp Technique; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012016:Reference Values; D016037:Single-Blind Method; D013851:Thinness; D013997:Time Factors
D001786:Blood Glucose; D016232:Endothelins; D007328:Insulin; D010919:Placebos