Sex-Specific Control of Fat Mass and Counterregulation by Hypothalamic Glucokinase.

Détails

ID Serval
serval:BIB_A295C7CD011C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Sex-Specific Control of Fat Mass and Counterregulation by Hypothalamic Glucokinase.
Périodique
Diabetes
Auteur(s)
Steinbusch L.K., Picard A., Bonnet M.S., Basco D., Labouèbe G., Thorens B.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
10/2016
Peer-reviewed
Oui
Volume
65
Numéro
10
Pages
2920-2931
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Glucokinase (Gck) is a critical regulator of glucose-induced insulin secretion by pancreatic β-cells. It has been suggested to also play an important role in glucose signaling in neurons of the ventromedial hypothalamic nucleus (VMN), a brain nucleus involved in the control of glucose homeostasis and feeding. To test the role of Gck in VMN glucose sensing and physiological regulation, we studied mice with genetic inactivation of the Gck gene in Sf1 neurons of the VMN (Sf1Gck(-/-) mice). Compared with control littermates, Sf1Gck(-/-) mice displayed increased white fat mass and adipocyte size, reduced lean mass, impaired hypoglycemia-induced glucagon secretion, and a lack of parasympathetic and sympathetic nerve activation by neuroglucopenia. However, these phenotypes were observed only in female mice. To determine whether Gck was required for glucose sensing by Sf1 neurons, we performed whole-cell patch clamp analysis of brain slices from control and Sf1Gck(-/-) mice. Absence of Gck expression did not prevent the glucose responsiveness of glucose-excited or glucose-inhibited Sf1 neurons in either sex. Thus Gck in the VMN plays a sex-specific role in the glucose-dependent control of autonomic nervous activity; this is, however, unrelated to the control of the firing activity of classical glucose-responsive neurons.

Mots-clé
Adipocytes/cytology, Adipocytes/drug effects, Adipocytes/metabolism, Animals, Female, Glucagon/metabolism, Glucokinase/genetics, Glucokinase/metabolism, Glucose/pharmacology, Homeostasis/drug effects, Hypothalamus/cytology, Hypothalamus/enzymology, Hypothalamus/metabolism, Male, Mice, Mice, Mutant Strains, Neurons/cytology, Neurons/drug effects, Neurons/metabolism, Patch-Clamp Techniques, Ventromedial Hypothalamic Nucleus/cytology, Ventromedial Hypothalamic Nucleus/enzymology, Ventromedial Hypothalamic Nucleus/metabolism
Pubmed
Open Access
Oui
Création de la notice
22/07/2016 11:51
Dernière modification de la notice
20/08/2019 16:08
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