α-cell glucokinase suppresses glucose-regulated glucagon secretion.

Détails

Ressource 1Télécharger: s41467-018-03034-0.pdf (1428.26 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_C69CB1A44E4C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
α-cell glucokinase suppresses glucose-regulated glucagon secretion.
Périodique
Nature communications
Auteur(s)
Basco D., Zhang Q., Salehi A., Tarasov A., Dolci W., Herrera P., Spiliotis I., Berney X., Tarussio D., Rorsman P., Thorens B.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
07/02/2018
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
546
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
Glucagon secretion by pancreatic α-cells is triggered by hypoglycemia and suppressed by high glucose levels; impaired suppression of glucagon secretion is a hallmark of both type 1 and type 2 diabetes. Here, we show that α-cell glucokinase (Gck) plays a role in the control of glucagon secretion. Using mice with α-cell-specific inactivation of Gck (αGckKO mice), we find that glucokinase is required for the glucose-dependent increase in intracellular ATP/ADP ratio and the closure of K javax.xml.bind.JAXBElement@dee6e8 channels in α-cells and the suppression of glucagon secretion at euglycemic and hyperglycemic levels. αGckKO mice display hyperglucagonemia in the fed state, which is associated with increased hepatic gluconeogenic gene expression and hepatic glucose output capacity. In adult mice, fed hyperglucagonemia is further increased and glucose intolerance develops. Thus, glucokinase governs an α-cell metabolic pathway that suppresses secretion at or above normoglycemic levels; abnormal suppression of glucagon secretion deregulates hepatic glucose metabolism and, over time, induces a pre-diabetic phenotype.

Mots-clé
Adenosine Diphosphate/metabolism, Adenosine Triphosphate/metabolism, Animals, Biological Transport, Female, Gene Expression, Glucagon/secretion, Glucagon-Secreting Cells/metabolism, Glucagon-Secreting Cells/pathology, Glucokinase/deficiency, Glucokinase/genetics, Glucose/metabolism, Glucose Intolerance/genetics, Glucose Intolerance/metabolism, Glucose Intolerance/pathology, Hypoglycemia/genetics, Hypoglycemia/metabolism, Hypoglycemia/pathology, Insulin/metabolism, KATP Channels/genetics, KATP Channels/metabolism, Liver/metabolism, Male, Mice, Mice, Knockout
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/02/2018 15:56
Dernière modification de la notice
20/08/2019 16:42
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