title: Gliotransmission and brain glucose sensing: critical role of endozepines.
abstract: Hypothalamic glucose sensing is involved in the control of feeding behavior and peripheral glucose homeostasis, and glial cells are suggested to play an important role in this process. Diazepam-binding inhibitor (DBI) and its processing product the octadecaneuropeptide (ODN), collectively named endozepines, are secreted by astroglia, and ODN is a potent anorexigenic factor. Therefore, we investigated the involvement of endozepines in brain glucose sensing. First, we showed that intracerebroventricular administration of glucose in rats increases DBI expression in hypothalamic glial-like tanycytes. We then demonstrated that glucose stimulates endozepine secretion from hypothalamic explants. Feeding experiments indicate that the anorexigenic effect of central administration of glucose was blunted by coinjection of an ODN antagonist. Conversely, the hyperphagic response elicited by central glucoprivation was suppressed by an ODN agonist. The anorexigenic effects of centrally injected glucose or ODN agonist were suppressed by blockade of the melanocortin-3/4 receptors, suggesting that glucose sensing involves endozepinergic control of the melanocortin pathway. Finally, we found that brain endozepines modulate blood glucose levels, suggesting their involvement in a feedback loop controlling whole-body glucose homeostasis. Collectively, these data indicate that endozepines are a critical relay in brain glucose sensing and potentially new targets in treatment of metabolic disorders.
authors.affiliation: INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Lanfray
authors.forename: Sébastien
authors.initials: S
authors.lastname: Arthaud
authors.forename: Johanne
authors.initials: J
authors.lastname: Ouellet
authors.forename: Vincent
authors.initials: V
authors.lastname: Compère
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Do Rego
authors.forename: Jérôme
authors.initials: J
authors.lastname: Leprince
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lefranc
authors.forename: Hélène
authors.initials: H
authors.lastname: Castel
authors.forename: Cynthia
authors.initials: C
authors.lastname: Bouchard
authors.forename: Boris
authors.initials: B
authors.lastname: Monge-Roffarello
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
authors.forename: Georges
authors.initials: G
authors.lastname: Pelletier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Tonon
authors.forename: Fabrice
authors.initials: F
authors.lastname: Morin
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects; D019167:Appetite Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D001070:Appetitive Behavior / Q000187:drug effects; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D026261:Diazepam Binding Inhibitor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D025461:Feedback, Physiological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D001067:Appetite Depressants; D019167:Appetite Stimulants; D026261:Diazepam Binding Inhibitor; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; D044101:Receptors, Melanocortin; C067529:diazepam binding inhibitor (33-50); D005947:Glucose