ArticleThe Journal of physiology2011
Orexin neurons as conditional glucosensors: paradoxical regulation of sugar sensing by intracellular fuels.
Article in The Journal of physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 68 citations in OpenAlex.
- Orexinergic responses to environmental stressors in the zebrafish gut.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2026Article
- Contribution of hypothalamic orexin (hypocretin) circuits to pathologies of motivation.British journal of pharmacology · 2024Review
- Interorgan rhythmicity as a feature of healthful metabolism.Cell metabolism · 2024Review
- The interrelationship between sleep, diet, and glucose metabolism.Sleep medicine reviews · 2023Review
- Glycemic Challenge Is Associated with the Rapid Cellular Activation of the Locus Ceruleus and Nucleus of Solitary Tract: Circumscribed Spatial Analysis of Phosphorylated MAP Kinase Immunoreactivity.Journal of clinical medicine · 2023Article
- Orexin and MCH neurons: regulators of sleep and metabolism.Frontiers in neuroscience · 2023Review
- The physiological control of eating: signals, neurons, and networks.Physiological reviews · 2022 · on this mapArticle
- Circadian Rhythms of the Hypothalamus: From Function to Physiology.Clocks & sleep · 2021Review
- The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa.Frontiers in psychiatry · 2021Article
- Neuropeptides as Primary Mediators of Brain Circuit Connectivity.Frontiers in neuroscience · 2021Review
- Control of Adipose Cell Browning and Its Therapeutic Potential.Metabolites · 2020Review
- The Central Role of Glucokinase in Glucose Homeostasis: A Perspective 50 Years After Demonstrating the Presence of the Enzyme in Islets of Langerhans.Frontiers in physiology · 2019Review
- Modulation of olfactory-driven behavior by metabolic signals: role of the piriform cortex.Brain structure & function · 2019Article
- Lateral Hypothalamic Area Neurotensin Neurons Are Required for Control of Orexin Neurons and Energy Balance.Endocrinology · 2018Article
- Role of Autonomic Nervous System and Orexinergic System on Adipose Tissue.Frontiers in physiology · 2017Review
- Early improvement in obstructive sleep apnea and increase in orexin levels after bariatric surgery in adolescents and young adults.Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery · 2017Observational
- Lactate as a Metabolite and a Regulator in the Central Nervous System.International journal of molecular sciences · 2016Review
- Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.The European journal of neuroscience · 2016Article
- Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons.American journal of physiology. Regulatory, integrative and comparative physiology · 2015Article
- Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats.Endocrinology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
Abstract
Central orexin/hypocretin neurons promote wakefulness, feeding and reward-seeking, and control blood glucose levels by regulating sympathetic outflow to the periphery. Glucose itself directly suppresses the electrical activity and cytosolic calcium levels of orexin cells. Recent in vitro studies suggested that glucose inhibition of orexin cells may be mechanistically unusual, because it persists under conditions where glucose metabolism is unlikely. To investigate this further, and to clarify whether background metabolic state regulates orexin cell glucosensing, here we analysed glucose responses of orexin cells in mouse brain slices, in the presence and absence of metabolic inhibitors and physiological energy substrates. Consistent with their documented insensitivity to glucokinase inhibitors, the glucose responses of orexin cells persisted in the presence of the mitochondrial poison oligomycin or the glial toxin fluoroacetate. Unexpectedly, in the presence of oligomycin, the magnitude of the glucose response was significantly enhanced. In turn, 2-deoxyglucose, a non-metabolizable glucose analogue, elicited larger responses than glucose. Conversely, intracellular pyruvate dose-dependently suppressed the glucose responses, an effect that was blocked by oligomycin. The glucose responses were also suppressed by intracellular lactate and ATP. Our new data suggest that other energy substrates not only fail to mimic the orexin glucose response, but paradoxically suppress it in a metabolism-dependent manner. We propose that this unexpected intrinsic property of orexin cells allows them to act as 'conditional glucosensors' that preferentially respond to glucose during reduced background energy levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.