A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_F3E314BF94F2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A Genetic Screen Identifies Hypothalamic Fgf15 as a Regulator of Glucagon Secretion.
Périodique
Cell reports
Auteur(s)
Picard A., Soyer J., Berney X., Tarussio D., Quenneville S., Jan M., Grouzmann E., Burdet F., Ibberson M., Thorens B.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
08/11/2016
Peer-reviewed
Oui
Volume
17
Numéro
7
Pages
1795-1806
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The counterregulatory response to hypoglycemia, which restores normal blood glucose levels to ensure sufficient provision of glucose to the brain, is critical for survival. To discover underlying brain regulatory systems, we performed a genetic screen in recombinant inbred mice for quantitative trait loci (QTL) controlling glucagon secretion in response to neuroglucopenia. We identified a QTL on the distal part of chromosome 7 and combined this genetic information with transcriptomic analysis of hypothalami. This revealed Fgf15 as the strongest candidate to control the glucagon response. Fgf15 was expressed by neurons of the dorsomedial hypothalamus and the perifornical area. Intracerebroventricular injection of FGF19, the human ortholog of Fgf15, reduced activation by neuroglucopenia of dorsal vagal complex neurons, of the parasympathetic nerve, and lowered glucagon secretion. In contrast, silencing Fgf15 in the dorsomedial hypothalamus increased neuroglucopenia-induced glucagon secretion. These data identify hypothalamic Fgf15 as a regulator of glucagon secretion.

Mots-clé
Aging, Animals, Chromosomes, Mammalian/metabolism, Deoxyglucose/pharmacology, Fibroblast Growth Factors/metabolism, Gene Silencing/drug effects, Genetic Testing, Genome, Glucagon/secretion, Hypothalamus/drug effects, Hypothalamus/metabolism, Mice, Inbred C57BL, Parasympathetic Nervous System/drug effects, Parasympathetic Nervous System/metabolism, Quantitative Trait Loci/genetics, FGF15, FGF19, QTL mapping, autonomic nervous system, dorsal vagal complex, genetic screen, glucagon secretion, glucose sensing, hypothalamus, neuroglucopenia
Pubmed
Web of science
Open Access
Oui
Création de la notice
30/11/2016 21:31
Dernière modification de la notice
20/08/2019 17:20
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