Hypothalamic apelin/reactive oxygen species signaling controls hepatic glucose metabolism in the onset of diabetes.

Détails

ID Serval
serval:BIB_CD30F16EE4FC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hypothalamic apelin/reactive oxygen species signaling controls hepatic glucose metabolism in the onset of diabetes.
Périodique
Antioxidants and Redox Signaling
Auteur(s)
Drougard A., Duparc T., Brenachot X., Carneiro L., Gouazé A., Fournel A., Geurts L., Cadoudal T., Prats A.C., Pénicaud L., Vieau D., Lesage J., Leloup C., Benani A., Cani P.D., Valet P., Knauf C.
ISSN
1557-7716 (Electronic)
ISSN-L
1523-0864
Statut éditorial
Publié
Date de publication
2014
Volume
20
Numéro
4
Pages
557-573
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
AIMS: We have previously demonstrated that central apelin is implicated in the control of peripheral glycemia, and its action depends on nutritional (fast versus fed) and physiological (normal versus diabetic) states. An intracerebroventricular (icv) injection of a high dose of apelin, similar to that observed in obese/diabetic mice, increase fasted glycemia, suggesting (i) that apelin contributes to the establishment of a diabetic state, and (ii) the existence of a hypothalamic to liver axis. Using pharmacological, genetic, and nutritional approaches, we aim at unraveling this system of regulation by identifying the hypothalamic molecular actors that trigger the apelin effect on liver glucose metabolism and glycemia.
RESULTS: We show that icv apelin injection stimulates liver glycogenolysis and gluconeogenesis via an over-activation of the sympathetic nervous system (SNS), leading to fasted hyperglycemia. The effect of central apelin on liver function is dependent of an increased production of hypothalamic reactive oxygen species (ROS). These data are strengthened by experiments using lentiviral vector-mediated over-expression of apelin in hypothalamus of mice that present over-activation of SNS associated to an increase in hepatic glucose production. Finally, we report that mice fed a high-fat diet present major alterations of hypothalamic apelin/ROS signaling, leading to activation of glycogenolysis. INNOVATION/CONCLUSION: These data bring compelling evidence that hypothalamic apelin is one master switch that participates in the onset of diabetes by directly acting on liver function. Our data support the idea that hypothalamic apelin is a new potential therapeutic target to treat diabetes.
Mots-clé
Animals, Autonomic Nervous System, Blood Glucose, Diabetes Mellitus, Type 2/metabolism, Gluconeogenesis, Glucose/metabolism, Glycogenolysis, Hypothalamus/metabolism, Intercellular Signaling Peptides and Proteins/physiology, Liver/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Obese, Reactive Oxygen Species/metabolism, Signal Transduction
Pubmed
Web of science
Création de la notice
20/10/2015 14:21
Dernière modification de la notice
20/08/2019 16:47
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