Fgf15 Neurons of the Dorsomedial Hypothalamus Control Glucagon Secretion and Hepatic Gluconeogenesis.

Détails

Ressource 1Télécharger: Picard et al., 2021.pdf (4845.67 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
ID Serval
serval:BIB_6BC81E235D09
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Fgf15 Neurons of the Dorsomedial Hypothalamus Control Glucagon Secretion and Hepatic Gluconeogenesis.
Périodique
Diabetes
Auteur(s)
Picard A., Metref S., Tarussio D., Dolci W., Berney X., Croizier S., Labouebe G., Thorens B.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
07/2021
Peer-reviewed
Oui
Volume
70
Numéro
7
Pages
1443-1457
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The counterregulatory response to hypoglycemia is an essential survival function. It is controlled by an integrated network of glucose-responsive neurons, which trigger endogenous glucose production to restore normoglycemia. The complexity of this glucoregulatory network is, however, only partly characterized. In a genetic screen of a panel of recombinant inbred mice we previously identified Fgf15, expressed in neurons of the dorsomedial hypothalamus (DMH), as a negative regulator of glucagon secretion. Here, we report on the generation of Fgf15 <sup>CretdTomato</sup> mice and their use to further characterize these neurons. We show that they were glutamatergic and comprised glucose-inhibited and glucose-excited neurons. When activated by chemogenetics, Fgf15 neurons prevented the increase in vagal nerve firing and the secretion of glucagon normally triggered by insulin-induced hypoglycemia. On the other hand, they increased the activity of the sympathetic nerve in the basal state and prevented its silencing by glucose overload. Higher sympathetic tone increased hepatic Creb1 phosphorylation, Pck1 mRNA expression, and hepatic glucose production leading to glucose intolerance. Thus, Fgf15 neurons of the DMH participate in the counterregulatory response to hypoglycemia by a direct adrenergic stimulation of hepatic glucose production while suppressing vagally induced glucagon secretion. This study provides new insights into the complex neuronal network that prevents the development of hypoglycemia.
Pubmed
Web of science
Open Access
Oui
Création de la notice
11/05/2021 9:46
Dernière modification de la notice
27/10/2021 6:10
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