title: Glucose regulates the effects of leptin on hypothalamic POMC neurons.
abstract: Leptin is believed to exert its potent appetite-suppressing effects via stimulation of hypothalamic anorexigenic proopiomelanocortin (POMC)-containing neurons and inhibition of orexigenic agouti-related protein (AgRP) neurons. We show here that at 11 mM glucose leptin excites POMC cells. At 5 mM glucose, however, leptin hyperpolarizes POMC neurons and suppresses action potential firing, by producing a greater decrease in excitatory synaptic tone than inhibitory tone. These results argue that when glucose is low (5 mM or less) AgRP neurons will be more important for mediating the anorectic effects of leptin than POMC cells. However, at high glucose concentrations (11 mM), activation of POMC cells may contribute to the appetite-suppressing effects of leptin. Our data also suggest the regulation of neuropeptide efficacy as a novel function of hypothalamic glucose sensing.
authors.affiliation: Henry Wellcome Center for Gene Function, Department of Physiology, Anatomy, and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Ma
authors.forename: Lejla
authors.initials: L
authors.lastname: Zubcevic
authors.forename: Frances M
authors.initials: FM
authors.lastname: Ashcroft
mesh_terms: D000818:Animals; D001069:Appetite Regulation; D001923:Brain Chemistry; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D007031:Hypothalamus / Q000166:cytology*; D020738:Leptin / Q000502:physiology*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D011333:Pro-Opiomelanocortin
chemical_list: D020738:Leptin; D011333:Pro-Opiomelanocortin; D005947:Glucose