Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.

Détails

ID Serval
serval:BIB_770094341DD3
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice.
Périodique
Endocrinology
Auteur(s)
Sartori C., Dessen P., Mathieu C., Monney A., Bloch J., Nicod P., Scherrer U., Duplain H.
ISSN
1945-7170[electronic]
Statut éditorial
Publié
Date de publication
10/2009
Peer-reviewed
Oui
Volume
150
Numéro
12
Pages
5311-5317
Langue
anglais
Résumé
Obesity and insulin resistance represent a problem of utmost clinical significance worldwide. Insulin-resistant states are characterized by the inability of insulin to induce proper signal transduction leading to defective glucose uptake in skeletal muscle tissue and impaired insulin-induced vasodilation. In various pathophysiological models, melatonin interacts with crucial molecules of the insulin signaling pathway, but its effects on glucose homeostasis are not known. In a diet-induced mouse model of insulin resistance and normal chow-fed control mice, we sought to assess the effects of an 8-wk oral treatment with melatonin on insulin and glucose tolerance and to understand underlying mechanisms. In high-fat diet-fed mice, but not in normal chow-fed control mice, melatonin significantly improved insulin sensitivity and glucose tolerance, as evidenced by a higher rate of glucose infusion to maintain euglycemia during hyperinsulinemic clamp studies and an attenuated hyperglycemic response to an ip glucose challenge. Regarding underlying mechanisms, we found that melatonin restored insulin-induced vasodilation to skeletal muscle, a major site of glucose utilization. This was due, at least in part, to the improvement of insulin signal transduction in the vasculature, as evidenced by increased insulin-induced phosphorylation of Akt and endoethelial nitric oxide synthase in aortas harvested from melatonin-treated high-fat diet-fed mice. In contrast, melatonin had no effect on the ability of insulin to promote glucose uptake in skeletal muscle tissue in vitro. These data demonstrate for the first time that in a diet-induced rodent model of insulin resistance, melatonin improves glucose homeostasis by restoring the vascular action of insulin.
Mots-clé
Animals, Blood Flow Velocity/drug effects, Blood Pressure/drug effects, Deoxyglucose/pharmacokinetics, Dietary Fats/administration & dosage, Endothelium, Vascular/drug effects, Endothelium, Vascular/metabolism, Glucose/metabolism, Glucose Tolerance Test, Heart Rate/drug effects, Homeostasis/drug effects, Insulin/blood, Insulin Resistance, Male, Melatonin/administration & dosage, Melatonin/pharmacology, Mice, Mice, Inbred C57BL, Muscle, Skeletal/blood supply, Muscle, Skeletal/drug effects, Nitric Oxide Synthase Type III/metabolism, Phosphorylation/drug effects, Proto-Oncogene Proteins c-akt/metabolism
Pubmed
Web of science
Création de la notice
02/10/2009 15:13
Dernière modification de la notice
03/03/2018 18:26
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