Hypertriglyceridemia and hyperinsulinemia are potent inducers of endothelin-1 release in humans

PierMarco Piatti, Lucilla D. Monti, Morena Conti, Laura Baruffaldi, Laura Galli, Chuong V. Phan, Barbara Guazzini, Antonio E. Pontiroli, Guido Pozza

Research output: Contribution to journalArticlepeer-review

Abstract

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 · kg-1 · 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, which 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.

Original languageEnglish
Pages (from-to)316-321
Number of pages6
JournalDiabetes
Volume45
Issue number3
Publication statusPublished - Mar 1996

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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