Gliotransmission and Brain Glucose Sensing
Critical Role of Endozepines
- Damien Lanfray1,2,3,
- Sébastien Arthaud2,3,4,
- Johanne Ouellet5,
- Vincent Compère1,2,3,6,
- Jean-Luc Do Rego1,2,3,
- Jérôme Leprince1,2,3,
- Benjamin Lefranc2,3,
- Hélène Castel1,2,3,
- Cynthia Bouchard7,
- Boris Monge-Roffarello7,
- Denis Richard7,
- Georges Pelletier5,
- Hubert Vaudry1,2,3,5,
- Marie-Christine Tonon1,2,3⇓ and
- Fabrice Morin1,2,3⇓
- 1INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France
- 2Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France
- 3University of Rouen, Mont-Saint-Aignan, France
- 4Centre National de la Recherche Scientifique Unité Mixte de Recherche 5167, University Claude Bernard Lyon 1, Lyon, France
- 5Research Center in Molecular Endocrinology, Oncology and Human Genomics, Laval University, Quebec, Quebec, Canada
- 6Department of Anaesthesiology and Critical Care, Rouen University Hospital, Rouen, France
- 7Centre de Recherche de l’Institut Universitaire de Cardiologie et Pneumologie de Québec, Laval University, Quebec, Quebec, Canada
- Corresponding author: Marie-Christine Tonon, , or Fabrice Morin, .
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.
- Received June 7, 2011.
- Accepted August 30, 2012.
- © 2013 by the American Diabetes Association.
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