Enhanced hypothalamic glucose sensing in obesity: alteration of redox signaling.

Détails

ID Serval
serval:BIB_BE73185AF943
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Enhanced hypothalamic glucose sensing in obesity: alteration of redox signaling.
Périodique
Diabetes
Auteur(s)
Colombani A.L., Carneiro L., Benani A., Galinier A., Jaillard T., Duparc T., Offer G., Lorsignol A., Magnan C., Casteilla L., Pénicaud L., Leloup C.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
2009
Volume
58
Numéro
10
Pages
2189-2197
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
OBJECTIVE: Recent data demonstrated that glucose sensing in different tissues is initiated by an intracellular redox signaling pathway in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the present study was to determine whether brain glucose hypersensitivity present in obese Zücker rats is related to an alteration in redox signaling.
RESEARCH DESIGN AND METHODS: Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus, changes in reactive oxygen species levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modifications of redox state and mitochondrial functions were assessed through oxidized glutathione, glutathione peroxidase, manganese superoxide dismutase, aconitase activities, and mitochondrial respiration.
RESULTS: Hypothalamic hypersensitivity to glucose was characterized by enhanced electrical activity of the arcuate nucleus and increased insulin secretion at a low glucose concentration, which does not produce such an effect in normal rats. It was associated with 1) increased reactive oxygen species levels in response to this low glucose load, 2) constitutive oxidized environment coupled with lower antioxidant enzyme activity at both the cellular and mitochondrial level, and 3) overexpression of several mitochondrial subunits of the respiratory chain coupled with a global dysfunction in mitochondrial activity. Moreover, pharmacological restoration of the glutathione hypothalamic redox state by reduced glutathione infusion in the third ventricle fully reversed the cerebral hypersensitivity to glucose.
CONCLUSIONS: The data demonstrated that obese Zücker rats' impaired hypothalamic regulation in terms of glucose sensing is linked to an abnormal redox signaling, which originates from mitochondria dysfunction.
Mots-clé
Aconitate Hydratase/metabolism, Action Potentials/drug effects, Animals, Brain/drug effects, Brain/physiology, Glucose/pharmacology, Homeostasis, Hypersensitivity/metabolism, Hypersensitivity/physiopathology, Hypothalamus/drug effects, Hypothalamus/physiology, Male, Mitochondria/drug effects, Mitochondria/physiology, Obesity/genetics, Obesity/physiopathology, Oxidation-Reduction, Oxidative Phosphorylation/drug effects, Oxygen Consumption/drug effects, Rats, Rats, Zucker, Signal Transduction
Pubmed
Open Access
Oui
Création de la notice
20/10/2015 13:20
Dernière modification de la notice
20/08/2019 15:32
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