Impaired glucose homeostasis in mice lacking the alpha1b-adrenergic receptor subtype.

Détails

ID Serval
serval:BIB_0DFE5C0BDD4B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Impaired glucose homeostasis in mice lacking the alpha1b-adrenergic receptor subtype.
Périodique
Journal of Biological Chemistry
Auteur(s)
Burcelin R., Uldry M., Foretz M., Perrin C., Dacosta A., Nenniger-Tosato M., Seydoux J., Cotecchia S., Thorens B.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2004
Volume
279
Numéro
2
Pages
1108-1115
Langue
anglais
Résumé
To assess the role of the alpha1b-adrenergic receptor (AR) in glucose homeostasis, we investigated glucose metabolism in knockout mice deficient of this receptor subtype (alpha1b-AR-/-). Mutant mice had normal blood glucose and insulin levels, but elevated leptin concentrations in the fed state. During the transition to fasting, glucose and insulin blood concentrations remained markedly elevated for at least 6 h and returned to control levels after 24 h whereas leptin levels remained high at all times. Hyperinsulinemia in the post-absorptive phase was normalized by atropine or methylatropine indicating an elevated parasympathetic activity on the pancreatic beta cells, which was associated with increased levels of hypothalamic NPY mRNA. Euglycemic clamps at both low and high insulin infusion rates revealed whole body insulin resistance with reduced muscle glycogen synthesis and impaired suppression of endogenous glucose production at the low insulin infusion rate. The liver glycogen stores were 2-fold higher in the fed state in the alpha1b-AR-/- compared with control mice, but were mobilized at the same rate during the fed to fast transition or following glucagon injections. Finally, high fat feeding for one month increased glucose intolerance and body weight in the alpha1b-AR-/-, but not in control mice. Altogether, our results indicate that in the absence of the alpha1b-AR the expression of hypotalamic NPY and the parasympathetic nervous activity are both increased resulting in hyperinsulinemia and insulin resistance as well as favoring obesity and glucose intolerance development during high fat feeding.
Mots-clé
Animals, Blood Glucose/metabolism, Body Weight, Glucagon/chemistry, Glucose/metabolism, Glycogen/metabolism, Homeostasis, Hyperinsulinism, Insulin Resistance, Leptin/metabolism, Liver/metabolism, Male, Mice, Mice, Mutant Strains, Mice, Obese, RNA, Messenger/metabolism, Receptors, Adrenergic/metabolism, Receptors, Adrenergic, alpha-1/genetics, Receptors, Adrenergic, alpha-1/physiology, Reverse Transcriptase Polymerase Chain Reaction, Time Factors
Pubmed
Web of science
Création de la notice
24/01/2008 11:05
Dernière modification de la notice
20/08/2019 12:35
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