Gliotransmission and Brain Glucose Sensing: Critical Role of Endozepines

Damien Lanfray (1) , Sébastien Arthaud (2) , Johanne Ouellet (3) , Vincent Compère (1) , Jean-Luc Do Rego , Jérôme Leprince (1) , Benjamin Lefranc (1) , Hélène Castel (1) , Cynthia Bouchard (3) , Boris Monge-Roffarello (3) , Denis Richard (4) , Georges Pelletier (5) , Hubert Vaudry , Marie-Christine Tonon (1) , Fabrice Morin (1)

1 DC2N - Différenciation et communication neuronale et neuroendocrine
2 Neuroendocrinologie cellulaire et moléculaire
3 ULaval - Université Laval [Québec]
4 LLAIC1 - Laboratoire de Logique, Algorithmique et Informatique
5 UR254 - Unité de Recherche en Génétique et Amélioration des Plantes

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.

Domaines: Chimie thérapeutique; Interactions cellulaires [q-bio.CB]; Neurobiologie; Pharmacologie

Damien Lanfray, Sébastien Arthaud, Johanne Ouellet, Vincent Compère, Jean-Luc Do Rego, et al.. Gliotransmission and Brain Glucose Sensing: Critical Role of Endozepines. Diabetes, 2013, 62 (3), pp.801-810. ⟨10.2337/db11-0785⟩. ⟨hal-01962799⟩