{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:55:21Z","timestamp":1792601721981,"version":"4.5.0"},"reference-count":41,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":3116,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,3,1]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.2337\/db11-0785","type":"journal-article","created":{"date-parts":[[2012,11,17]],"date-time":"2012-11-17T06:37:53Z","timestamp":1353134273000},"page":"801-810","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":82,"title":["Gliotransmission and Brain Glucose Sensing"],"prefix":"10.2337","volume":"62","author":[{"given":"Damien","family":"Lanfray","sequence":"first","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Arthaud","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"},{"name":"Centre National de la Recherche Scientifique Unit\u00e9 Mixte de Recherche 5167, University Claude Bernard Lyon 1, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanne","family":"Ouellet","sequence":"additional","affiliation":[{"name":"Research Center in Molecular Endocrinology, Oncology and Human Genomics, Laval University, Quebec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Comp\u00e8re","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"},{"name":"Department of Anaesthesiology and Critical Care, Rouen University Hospital, Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Do Rego","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Leprince","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Lefranc","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Castel","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et Pneumologie de Qu\u00e9bec, Laval University, Quebec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boris","family":"Monge-Roffarello","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et Pneumologie de Qu\u00e9bec, Laval University, Quebec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Richard","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et Pneumologie de Qu\u00e9bec, Laval University, Quebec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Pelletier","sequence":"additional","affiliation":[{"name":"Research Center in Molecular Endocrinology, Oncology and Human Genomics, Laval University, Quebec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Vaudry","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"},{"name":"Research Center in Molecular Endocrinology, Oncology and Human Genomics, Laval University, Quebec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Tonon","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Morin","sequence":"additional","affiliation":[{"name":"INSERM U982, DC2N Laboratory of Neuronal and Neuroendocrine Cell Differentiation and Communication, Mont-Saint-Aignan, France"},{"name":"Institute for Biomedical Research and Innovation, Regional Platform for Cell Imaging (PRIMACEN), Rouen, France"},{"name":"University of Rouen, Mont-Saint-Aignan, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2013,2,14]]},"reference":[{"key":"2022031210153434100_B1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbr.2009.12.024","article-title":"Hypothalamic nutrient sensing in the control of energy homeostasis","volume":"209","author":"Blouet","year":"2010","journal-title":"Behav Brain Res"},{"key":"2022031210153434100_B2","doi-asserted-by":"crossref","first-page":"4428","DOI":"10.1210\/endo.139.10.6332","article-title":"A C-terminal fragment of Agouti-related protein increases feeding and antagonizes the effect of \u03b1-melanocyte stimulating hormone in vivo","volume":"139","author":"Rossi","year":"1998","journal-title":"Endocrinology"},{"key":"2022031210153434100_B3","doi-asserted-by":"crossref","first-page":"3940","DOI":"10.1073\/pnas.82.11.3940","article-title":"Neuropeptide Y injected in the paraventricular hypothalamus: a powerful stimulant of feeding behavior","volume":"82","author":"Stanley","year":"1985","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031210153434100_B4","doi-asserted-by":"crossref","first-page":"988","DOI":"10.2337\/diabetes.55.04.06.db05-1386","article-title":"Evidence from glut2-null mice that glucose is a critical physiological regulator of feeding","volume":"55","author":"Bady","year":"2006","journal-title":"Diabetes"},{"key":"2022031210153434100_B5","doi-asserted-by":"crossref","first-page":"3545","DOI":"10.1172\/JCI26309","article-title":"Regulation of glucagon secretion by glucose transporter type 2 (glut2) and astrocyte-dependent glucose sensors","volume":"115","author":"Marty","year":"2005","journal-title":"J Clin Invest"},{"key":"2022031210153434100_B6","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1152\/ajplegacy.1975.229.5.1438","article-title":"Feeding induced by intracerebroventricular 2-deoxy-D-glucose in the rat","volume":"229","author":"Miselis","year":"1975","journal-title":"Am J Physiol"},{"key":"2022031210153434100_B7","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1152\/ajplegacy.1969.217.4.1083","article-title":"Increased feeding in response to decreased glucose utilization in the rat and monkey","volume":"217","author":"Smith","year":"1969","journal-title":"Am J Physiol"},{"key":"2022031210153434100_B8","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nature06098","article-title":"Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity","volume":"449","author":"Parton","year":"2007","journal-title":"Nature"},{"key":"2022031210153434100_B9","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.2337\/db07-0193","article-title":"Glucose ingestion fails to inhibit hypothalamic neuronal activity in patients with type 2 diabetes","volume":"56","author":"Vidarsdottir","year":"2007","journal-title":"Diabetes"},{"key":"2022031210153434100_B10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1046\/j.1471-4159.2003.01892.x","article-title":"Hypothalamic ependymal-glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing","volume":"86","author":"Garc\u00eda","year":"2003","journal-title":"J Neurochem"},{"key":"2022031210153434100_B11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1210\/endo.141.1.7234","article-title":"Localization of glucokinase-like immunoreactivity in the rat lower brain stem: for possible location of brain glucose-sensing mechanisms","volume":"141","author":"Maekawa","year":"2000","journal-title":"Endocrinology"},{"key":"2022031210153434100_B12","doi-asserted-by":"crossref","first-page":"e00035","DOI":"10.1042\/AN20090059","article-title":"Glial glucokinase expression in adult and post-natal development of the hypothalamic region","volume":"2","author":"Mill\u00e1n","year":"2010","journal-title":"ASN Neuro"},{"key":"2022031210153434100_B13","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1113\/jphysiol.2010.202051","article-title":"ATP-mediated glucosensing by hypothalamic tanycytes","volume":"589","author":"Frayling","year":"2011","journal-title":"J Physiol"},{"key":"2022031210153434100_B14","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1002\/glia.21246","article-title":"Glucose increases intracellular free Ca(2+) in tanycytes via ATP released through connexin 43 hemichannels","volume":"60","author":"Orellana","year":"2012","journal-title":"Glia"},{"key":"2022031210153434100_B15","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.2337\/diabetes.53.5.1230","article-title":"Third ventricular alloxan reversibly impairs glucose counterregulatory responses","volume":"53","author":"Sanders","year":"2004","journal-title":"Diabetes"},{"key":"2022031210153434100_B16","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.2337\/db11-0120","article-title":"Glucose transporter-1 in the hypothalamic glial cells mediates glucose sensing to regulate glucose production in vivo","volume":"60","author":"Chari","year":"2011","journal-title":"Diabetes"},{"key":"2022031210153434100_B17"},{"key":"2022031210153434100_B18","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1677\/JME-09-0176","article-title":"Acute food deprivation reduces expression of diazepam-binding inhibitor, the precursor of the anorexigenic octadecaneuropeptide ODN, in mouse glial cells","volume":"44","author":"Comp\u00e8re","year":"2010","journal-title":"J Mol Endocrinol"},{"key":"2022031210153434100_B19","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0143-4179(90)90155-R","article-title":"Immunocytochemical localization of the endogenous benzodiazepine ligand octadecaneuropeptide (ODN) in the rat brain","volume":"15","author":"Tonon","year":"1990","journal-title":"Neuropeptides"},{"key":"2022031210153434100_B20","doi-asserted-by":"crossref","first-page":"21359","DOI":"10.1074\/jbc.M110.105858","article-title":"Pregnenolone sulfate and cortisol induce secretion of acyl-CoA-binding protein and its conversion into endozepines from astrocytes","volume":"285","author":"Loomis","year":"2010","journal-title":"J Biol Chem"},{"key":"2022031210153434100_B21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1096\/fj.02-0317com","article-title":"Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates endozepine release from cultured rat astrocytes via a PKA-dependent mechanism","volume":"17","author":"Masmoudi","year":"2003","journal-title":"FASEB J"},{"key":"2022031210153434100_B22","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/(SICI)1098-1136(19990215)25:4<404::AID-GLIA9>3.0.CO;2-Q","article-title":"GABA inhibits endozepine release from cultured rat astrocytes","volume":"25","author":"Patte","year":"1999","journal-title":"Glia"},{"key":"2022031210153434100_B23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0014-2999(01)00771-3","article-title":"The octadecaneuropeptide [diazepam-binding inhibitor (33-50)] exerts potent anorexigenic effects in rodents","volume":"414","author":"de Mateos-Verchere","year":"2001","journal-title":"Eur J Pharmacol"},{"key":"2022031210153434100_B24","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1038\/sj.npp.1301280","article-title":"Pharmacological characterization of the receptor mediating the anorexigenic action of the octadecaneuropeptide: evidence for an endozepinergic tone regulating food intake","volume":"32","author":"do Rego","year":"2007","journal-title":"Neuropsychopharmacology"},{"key":"2022031210153434100_B25","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1046\/j.1365-2826.2003.00970.x","article-title":"Effect of intracerebroventricular administration of the octadecaneuropeptide on the expression of pro-opiomelanocortin, neuropeptide Y and corticotropin-releasing hormone mRNAs in rat hypothalamus","volume":"15","author":"Comp\u00e8re","year":"2003","journal-title":"J Neuroendocrinol"},{"key":"2022031210153434100_B26","doi-asserted-by":"crossref","first-page":"2342","DOI":"10.1210\/en.2008-1432","article-title":"The orexigenic activity of the hypothalamic neuropeptide 26RFa is mediated by the neuropeptide Y and proopiomelanocortin neurons of the arcuate nucleus","volume":"150","author":"Lectez","year":"2009","journal-title":"Endocrinology"},{"key":"2022031210153434100_B27","doi-asserted-by":"crossref","first-page":"6045","DOI":"10.1046\/j.0014-2956.2001.02533.x","article-title":"Synthesis, conformational analysis and biological activity of cyclic analogs of the octadecaneuropeptide ODN. Design of a potent endozepine antagonist","volume":"268","author":"Leprince","year":"2001","journal-title":"Eur J Biochem"},{"key":"2022031210153434100_B28","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/0306-4522(93)90023-9","article-title":"Ontogeny of diazepam-binding inhibitor-related peptides (endozepines) in the rat brain","volume":"57","author":"Malagon","year":"1993","journal-title":"Neuroscience"},{"key":"2022031210153434100_B29","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/0031-9384(86)90295-7","article-title":"D-glucose suppression of eating after intra-third ventricle infusion in rat","volume":"37","author":"Kurata","year":"1986","journal-title":"Physiol Behav"},{"key":"2022031210153434100_B30","doi-asserted-by":"crossref","first-page":"16871","DOI":"10.1073\/pnas.0809255105","article-title":"Differential effects of central fructose and glucose on hypothalamic malonyl-CoA and food intake","volume":"105","author":"Cha","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022031210153434100_B31","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1177\/153537020322801009","article-title":"Intracerebroventricular administration of insulin and glucose inhibits the anorectic action of leptin in rats","volume":"228","author":"Fujita","year":"2003","journal-title":"Exp Biol Med (Maywood)"},{"key":"2022031210153434100_B32","doi-asserted-by":"crossref","first-page":"3454","DOI":"10.1021\/jm00018a005","article-title":"Cyclic lactam alpha-melanotropin analogues of Ac-Nle4-cyclo[Asp5, D-Phe7,Lys10] alpha-melanocyte-stimulating hormone-(4-10)-NH2 with bulky aromatic amino acids at position 7 show high antagonist potency and selectivity at specific melanocortin receptors.","volume":"38","author":"Hruby","year":"1995","journal-title":"J Med Chem"},{"key":"2022031210153434100_B33","doi-asserted-by":"crossref","first-page":"180","DOI":"10.2337\/diab.44.2.180","article-title":"Local ventromedial hypothalamus glucopenia triggers counterregulatory hormone release","volume":"44","author":"Borg","year":"1995","journal-title":"Diabetes"},{"key":"2022031210153434100_B34","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1126\/science.1112085","article-title":"Regulation of blood glucose by hypothalamic pyruvate metabolism","volume":"309","author":"Lam","year":"2005","journal-title":"Science"},{"key":"2022031210153434100_B35","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1038\/35078085","article-title":"Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus","volume":"411","author":"Cowley","year":"2001","journal-title":"Nature"},{"key":"2022031210153434100_B36","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/nn.2167","article-title":"Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance","volume":"11","author":"Tong","year":"2008","journal-title":"Nat Neurosci"},{"key":"2022031210153434100_B37","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1038\/nrg862","article-title":"Genetic approaches to studying energy balance: perception and integration","volume":"3","author":"Barsh","year":"2002","journal-title":"Nat Rev Genet"},{"key":"2022031210153434100_B38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev.nutr.24.012003.132428","article-title":"The critical role of the melanocortin system in the control of energy balance","volume":"24","author":"Seeley","year":"2004","journal-title":"Annu Rev Nutr"},{"key":"2022031210153434100_B39","doi-asserted-by":"crossref","first-page":"10128","DOI":"10.1523\/JNEUROSCI.18-23-10128.1998","article-title":"Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight","volume":"18","author":"Grill","year":"1998","journal-title":"J Neurosci"},{"key":"2022031210153434100_B40","doi-asserted-by":"crossref","first-page":"E252","DOI":"10.1152\/ajpendo.00451.2006","article-title":"Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss","volume":"293","author":"Li","year":"2007","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031210153434100_B41","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cmet.2004.12.004","article-title":"The hypothalamic arcuate nucleus: a key site for mediating leptin\u2019s effects on glucose homeostasis and locomotor activity","volume":"1","author":"Coppari","year":"2005","journal-title":"Cell Metab"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/62\/3\/801\/569764\/801.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/62\/3\/801\/569764\/801.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:27:26Z","timestamp":1667406446000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/62\/3\/801\/15562\/Gliotransmission-and-Brain-Glucose-SensingCritical"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,14]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2013,2,14]]},"published-print":{"date-parts":[[2013,3,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db11-0785","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,14]]}}}