Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require AMPK-Induced Txn2 Expression but Are Dispensable for Physiological Counterregulation.

Détails

Ressource 1Télécharger: Quenneville et al., Diabetes 2020.pdf (2455.65 [Ko])
Etat: Public
Version: de l'auteur
Licence: Non spécifiée
ID Serval
serval:BIB_8D8A4D281085
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require AMPK-Induced Txn2 Expression but Are Dispensable for Physiological Counterregulation.
Périodique
Diabetes
Auteur(s)
Quenneville S., Labouèbe G., Basco D., Metref S., Viollet B., Foretz M., Thorens B.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
11/2020
Peer-reviewed
Oui
Volume
69
Numéro
11
Pages
2253-2266
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The ventromedial nucleus of the hypothalamus (VMN) is involved in the counterregulatory response to hypoglycemia. VMN neurons activated by hypoglycemia (glucose-inhibited [GI] neurons) have been assumed to play a critical although untested role in this response. Here, we show that expression of a dominant negative form of AMPK or inactivation of AMPK α1 and α2 subunit genes in Sf1 neurons of the VMN selectively suppressed GI neuron activity. We found that Txn2, encoding a mitochondrial redox enzyme, was strongly downregulated in the absence of AMPK activity and that reexpression of Txn2 in Sf1 neurons restored GI neuron activity. In cell lines, Txn2 was required to limit glucopenia-induced reactive oxygen species production. In physiological studies, absence of GI neuron activity after AMPK suppression in the VMN had no impact on the counterregulatory hormone response to hypoglycemia or on feeding. Thus, AMPK is required for GI neuron activity by controlling the expression of the antioxidant enzyme Txn2. However, the glucose-sensing capacity of VMN GI neurons is not required for the normal counterregulatory response to hypoglycemia. Instead, it may represent a fail-safe system in case of impaired hypoglycemia sensing by peripherally located glucose detection systems that are connected to the VMN.
Pubmed
Web of science
Création de la notice
02/09/2020 11:26
Dernière modification de la notice
15/01/2021 8:10
Données d'usage