title: Hypoglycemia-activated GLUT2 neurons of the nucleus tractus solitarius stimulate vagal activity and glucagon secretion.
abstract: Glucose-sensing neurons in the brainstem participate in the regulation of energy homeostasis but have been poorly characterized because of the lack of specific markers to identify them. Here we show that GLUT2-expressing neurons of the nucleus of the tractus solitarius form a distinct population of hypoglycemia-activated neurons. Their response to low glucose is mediated by reduced intracellular glucose metabolism, increased AMP-activated protein kinase activity, and closure of leak K(+) channels. These are GABAergic neurons that send projections to the vagal motor nucleus. Light-induced stimulation of channelrhodospin-expressing GLUT2 neurons in vivo led to increased parasympathetic nerve firing and glucagon secretion. Thus GLUT2 neurons of the nucleus tractus solitarius link hypoglycemia detection to counterregulatory response. These results may help identify the cause of hypoglycemia-associated autonomic failure, a major threat in the insulin treatment of diabetes.
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, rue du Bugnon 9, 1005 Lausanne, Switzerland; Department of Medicine, University of Fribourg, Rte Albert Gockel 1, 1700 Fribourg, Switzerland.
authors.forename: Christophe M
authors.initials: CM
authors.lastname: Lamy
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode Building, 1015 Lausanne, Switzerland.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sanno
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode Building, 1015 Lausanne, Switzerland.
authors.forename: Gwenaël
authors.initials: G
authors.lastname: Labouèbe
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode Building, 1015 Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Picard
authors.affiliation: CNRS-University Paris Diderot, Case courrier 7126, 4 rue Marie Andrée Lagroua Weill-Halle, 75205 Paris Cedex 13, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
authors.affiliation: Department of Fundamental Neurosciences, University of Lausanne, rue du Bugnon 9, 1005 Lausanne, Switzerland. Electronic address: jean-yves.chatton@unil.ch.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Chatton
authors.affiliation: Center for Integrative Genomics, University of Lausanne, Genopode Building, 1015 Lausanne, Switzerland. Electronic address: bernard.thorens@unil.ch.
authors.forename: Bernard
authors.initials: B
authors.lastname: Thorens
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D000075402:Channelrhodopsins; D003847:Deoxyglucose / Q000494:pharmacology; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D005934:Glucagon / Q000378:metabolism*; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism / Q000473:pathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D017552:Solitary Nucleus / Q000502:physiology*
chemical_list: D000075402:Channelrhodopsins; D051273:Glucose Transporter Type 2; D015221:Potassium Channels; D005934:Glucagon; D003847:Deoxyglucose; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D005944:Glucosamine