Gliotransmission and Brain Glucose Sensing
Copyright policy )Gliotransmission and Brain Glucose Sensing
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.
- Institute of Research and Innovation France
- Claude Bernard University Lyon 1 France
- Université Laval Canada
- Normandie Université France
- Clermont Université France
Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Wistar, Appetite Stimulants, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Neuropeptides, Synaptic Transmission, MESH: Arcuate Nucleus of Hypothalamus, MESH: Appetitive Behavior, Tissue Culture Techniques, MESH: Appetite Depressants, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Receptors, MESH: Animals, MESH: Nerve Tissue Proteins, MESH: Peptide Fragments, Diazepam Binding Inhibitor, Feedback, Physiological, Appetitive Behavior, MESH: Appetite Stimulants, MESH: Feedback, Receptors, Melanocortin, MESH: Gene Expression Regulation, MESH: Glucose, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Melanocortin, MESH: Neuroglia, Neuroglia, Signal Transduction, MESH: Rats, Physiological, Intraventricular, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Hypothalamus, 610, Nerve Tissue Proteins, MESH: Protein Processing, Appetite Depressants, MESH: Synaptic Transmission, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Injections, Animals, MESH: Tissue Culture Techniques, Rats, Wistar, Molecular Biology, Injections, Intraventricular, Appetite Regulation, Neuropeptides, Post-Translational, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Arcuate Nucleus of Hypothalamus, MESH: Hypothalamus, MESH: Male, Peptide Fragments, Rats, Glucose, Gene Expression Regulation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, Protein Processing, Post-Translational, MESH: Appetite Regulation
Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Wistar, Appetite Stimulants, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Neuropeptides, Synaptic Transmission, MESH: Arcuate Nucleus of Hypothalamus, MESH: Appetitive Behavior, Tissue Culture Techniques, MESH: Appetite Depressants, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Receptors, MESH: Animals, MESH: Nerve Tissue Proteins, MESH: Peptide Fragments, Diazepam Binding Inhibitor, Feedback, Physiological, Appetitive Behavior, MESH: Appetite Stimulants, MESH: Feedback, Receptors, Melanocortin, MESH: Gene Expression Regulation, MESH: Glucose, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Melanocortin, MESH: Neuroglia, Neuroglia, Signal Transduction, MESH: Rats, Physiological, Intraventricular, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, Hypothalamus, 610, Nerve Tissue Proteins, MESH: Protein Processing, Appetite Depressants, MESH: Synaptic Transmission, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Injections, Animals, MESH: Tissue Culture Techniques, Rats, Wistar, Molecular Biology, Injections, Intraventricular, Appetite Regulation, Neuropeptides, Post-Translational, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Arcuate Nucleus of Hypothalamus, MESH: Hypothalamus, MESH: Male, Peptide Fragments, Rats, Glucose, Gene Expression Regulation, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, Protein Processing, Post-Translational, MESH: Appetite Regulation
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