Short-term administration of isotretinoin elevates plasma triglyceride concentrations without affecting insulin sensitivity in healthy humans

Détails

ID Serval
serval:BIB_F6836ABDC868
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Short-term administration of isotretinoin elevates plasma triglyceride concentrations without affecting insulin sensitivity in healthy humans
Périodique
Metabolism: Clinical and Experimental
Auteur(s)
Stoll  D., Binnert  C., Mooser  V., Tappy  L.
ISSN
0026-0495 (Print)
Statut éditorial
Publié
Date de publication
01/2004
Volume
53
Numéro
1
Pages
4-10
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan
Résumé
The mechanism underlying hypertriglyceridemia-associated insulin resistance in humans remains poorly understood. It has been proposed that hypertriglyceridemia only produces insulin resistance when associated with an increased lipid delivery to muscle. Accordingly, hypertriglyceridemia secondary to a decreased clearance of triglyceride-rich particles should not cause insulin resistance. To verify this hypothesis, we assessed whole body and adipose tissue insulin sensitivity in 15 healthy male volunteers before and after a 5-day administration of isotretinoin (1 mg/kg/d), a vitamin A derivative that decreases the clearance of triglyceride-rich particles. Whole body insulin-mediated glucose disposal (6,6 (2)H(2)glucose), glucose oxidation (indirect calorimetry), lipolysis ((2)H(5) glycerol), and subcutaneous adipose lipolysis (microdialysis) were evaluated during a 3-step hyperinsulinemic euglycemic clamp. Isotretinoin increased plasma triglyceride from 0.97 +/- 0.15 to 1.30 +/- 0.22 mmol/L (P <.02), but did not change whole body insulin-mediated glucose disposal and lipolysis. These observations are consistent with an isotretinoin-induced inhibition of very-low-density lipoprotein (VLDL)-triglyceride clearance. The suppression of endogenous glucose production and the reduction in subcutaneous adipose glycerol concentrations by insulin remained equally unaffected after isotretinoin administration. We conclude that the impaired clearance of triglyceride-rich particles secondary to a 5-day isotretinoin administration does not impair insulin-mediated antilipolysis or glucose disposal. The data support the concept that hypertriglyceridemia-associated insulin resistance develops primarily when triglyceride production is increased.
Mots-clé
Adipose Tissue/chemistry/drug effects/metabolism Adult Blood Glucose/metabolism Calorimetry, Indirect Deuterium Epinephrine/diagnostic use Fasting Glucose Clamp Technique Glycerol/analysis/blood Humans Hypertriglyceridemia/complications Insulin/blood/pharmacology *Insulin Resistance Isotretinoin/*administration & dosage Kinetics Lipolysis/drug effects Lipoproteins, VLDL/blood Male Microdialysis Oxidation-Reduction Triglycerides/biosynthesis/*blood
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 14:36
Dernière modification de la notice
20/08/2019 17:22
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