Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans.
The purpose of the study was to evaluate fasting endothelin-1 levels in subjects with syndrome X, in subjects with insulinoma, and in normal subjects. The single and synergistic contributions of insulin and triglyceride levels to endothelin-1 release were studied in normal subjects. This was achieved by the evaluation of endothelin-1 levels in response to an insulin bolus combined with a euglycemic clamp (protocol A) and during intralipid (test 1) or saline (test 2) infusions lasting 360 min (protocol B). In protocol B, a euglycemic two-step hyperinsulinemic (25 and 125 mU x kg-1 x h-1) clamp was started at 120 min. Subjects with syndrome X showed significantly higher endothelin-1 levels than normal subjects and subjects with insulinoma (7.22 +/- 0.89 vs. 2.61 +/- 0.38 and 2.49 +/- 0.24 pg/ml, P < 0.01). After an insulin bolus, endothelin-1 levels peaked at 10 min (3.71 +/- 0.96 pg/ml). The incremental area of endothelin-1 was significantly higher after insulin than after a saline bolus. In test 1, an acute increase in triglyceride levels significantly enhanced endothelin-1 levels, with were further increased by the synergistic contribution of high insulin and triglyceride levels. In test 2, endothelin-1 release was achieved at high insulin levels but remained significantly lower than in test 1. In conclusion, subjects with syndrome X showed higher endothelin-1 levels than normal subjects and subjects with insulinoma. These levels were reproduced in normal subjects by a simultaneous increase in insulin and triglyceride levels.
Piatti
P M
PM
Istituto Scientifico H. San Raffaele, Cattedra di Clinica Medica, University of Milan, Italy.
Monti
L D
LD
Conti
M
M
Baruffaldi
L
L
Galli
L
L
Phan
C V
CV
Guazzini
B
B
Pontiroli
A E
AE
Pozza
G
G
D000328:Adult; D001794:Blood Pressure; D016232:Endothelins / Q000097:blood*; D005217:Fat Emulsions, Intravenous; D005260:Female; D015309:Glucose Clamp Technique; D006339:Heart Rate; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007328:Insulin / Q000097:blood*; D007340:Insulinoma / Q000097:blood; D007700:Kinetics; D008297:Male; D017566:Microvascular Angina / Q000097:blood*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood
D016232:Endothelins; D005217:Fat Emulsions, Intravenous; D007328:Insulin