title: ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis.
abstract: Glucose-responsive (GR) neurons in the hypothalamus are thought to be critical in glucose homeostasis, but it is not known how they function in this context. Kir6.2 is the pore-forming subunit of K(ATP) channels in many cell types, including pancreatic beta-cells and heart. Here we show the complete absence of both functional ATP-sensitive K+ (K(ATP)) channels and glucose responsiveness in the neurons of the ventromedial hypothalamus (VMH) in Kir6.2-/- mice. Although pancreatic alpha-cells were functional in Kir6.2-/-, the mice exhibited a severe defect in glucagon secretion in response to systemic hypoglycemia. In addition, they showed a complete loss of glucagon secretion, together with reduced food intake in response to neuroglycopenia. Thus, our results demonstrate that KATP channels are important in glucose sensing in VMH GR neurons, and are essential for the maintenance of glucose homeostasis.
authors.affiliation: Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miki
authors.forename: B
authors.initials: B
authors.lastname: Liss
authors.forename: K
authors.initials: K
authors.lastname: Minami
authors.forename: T
authors.initials: T
authors.lastname: Shiuchi
authors.forename: A
authors.initials: A
authors.lastname: Saraya
authors.forename: Y
authors.initials: Y
authors.lastname: Kashima
authors.forename: M
authors.initials: M
authors.lastname: Horiuchi
authors.forename: F
authors.initials: F
authors.lastname: Ashcroft
authors.forename: Y
authors.initials: Y
authors.lastname: Minokoshi
authors.forename: J
authors.initials: J
authors.lastname: Roeper
authors.forename: S
authors.initials: S
authors.lastname: Seino
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D004435:Eating / Q000502:physiology; D004594:Electrophysiology; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006728:Hormones / Q000494:pharmacology; D007003:Hypoglycemia / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000502:physiology*; D066298:In Vitro Techniques; D054086:KATP Channels; D051379:Mice; D018345:Mice, Knockout; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D002395:Catecholamines; D006728:Hormones; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D005934:Glucagon; D005947:Glucose; D004837:Epinephrine