Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice

Abstract : Recent studies have shown that the hypothalamic neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and increasing insulin sensitivity. In this study, we further characterized the role of the 26RFa/GPR103 peptidergic system in the global regulation of glucose homeostasis using a 26RFa receptor antagonist, and also assessed whether a dysfunction of the 26RFa/GPR103 system occurs in obese hyperglycemic mice. Firstly, we demonstrate that administration of the GPR103 antagonist reduces the global glucose-induced incretin effect and insulin sensitivity whereas, conversely, administration of exogenous 26RFa attenuates glucose-induced hyperglycemia. Using a mouse model of high-fat diet-induced obesity and hyperglycemia, we found a loss of the anti-hyperglcemic effect and insulinotropic activity of 26RFa, accompanied with a marked reduction of its insulin-sensitive effect. Interestingly, this resistance to 26RFa is associated with a down-regulation of the 26RFa receptor in the pancreatic islets, and insulin target tissues. Finally, we observed that the production and release kinetics of 26RFa after an oral glucose challenge is profoundly altered in the high-fat mice. Altogether, the present findings support the view that 26RFa is a key regulator of glucose homeostasis whose activity is markedly altered under obese/hyperglycemic conditions.
Type de document :
Article dans une revue
Liste complète des métadonnées

https://hal-normandie-univ.archives-ouvertes.fr/hal-02330443
Contributeur : Nicolas Chartrel <>
Soumis le : mercredi 27 mai 2020 - 02:32:07
Dernière modification le : jeudi 28 mai 2020 - 14:14:37

Fichier

2019_prevost_am_j_physiol_endo...
Fichiers produits par l'(les) auteur(s)

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Citation

Gaëtan Prévost, Arnaud Arabo, Marie-Anne Le Solliec, Justine Bons, Marie Picot, et al.. Neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice. AJP - Endocrinology and Metabolism, American Physiological Society, 2019, 317 (1), pp.E147-E157. ⟨10.1152/ajpendo.00540.2018⟩. ⟨hal-02330443⟩

Partager

Métriques

Consultations de la notice

105

Téléchargements de fichiers

30