title: Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice.
abstract: Glucose homeostasis is critically dependent on insulin release from pancreatic beta-cells, which is strictly regulated by glucose-induced oscillations in membrane potential (V(m)) and the cytosolic calcium level ([Ca(2+)](cyt)). We propose that TRPM5, a Ca(2+)-activated monovalent cation channel, is a positive regulator of glucose-induced insulin release. Immunofluorescence revealed expression of TRPM5 in pancreatic islets. A Ca(2+)-activated nonselective cation current with TRPM5-like properties is significantly reduced in Trpm5(-/-) cells. Ca(2+)-imaging and electrophysiological analysis show that glucose-induced oscillations of V(m) and [Ca(2+)](cyt) have on average a reduced frequency in Trpm5(-/-) islets, specifically due to a lack of fast oscillations. As a consequence, glucose-induced insulin release from Trpm5(-/-) pancreatic islets is significantly reduced, resulting in an impaired glucose tolerance in Trpm5(-/-) mice.
authors.affiliation: Laboratory of Ion Channel Research and Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, B-3001 Louvain, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Colsoul
authors.forename: Anica
authors.initials: A
authors.lastname: Schraenen
authors.forename: Katleen
authors.initials: K
authors.lastname: Lemaire
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
authors.forename: Leentje
authors.initials: L
authors.lastname: Van Lommel
authors.forename: Andrei
authors.initials: A
authors.lastname: Segal
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Owsianik
authors.forename: Karel
authors.initials: K
authors.lastname: Talavera
authors.forename: Thomas
authors.initials: T
authors.lastname: Voets
authors.forename: Robert F
authors.initials: RF
authors.lastname: Margolskee
authors.forename: Zaza
authors.initials: Z
authors.lastname: Kokrashvili
authors.forename: Patrick
authors.initials: P
authors.lastname: Gilon
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Frans C
authors.initials: FC
authors.lastname: Schuit
authors.forename: Rudi
authors.initials: R
authors.lastname: Vennekens
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002412:Cations; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010641:Phenotype; D050053:TRPM Cation Channels / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D002412:Cations; D007328:Insulin; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; D005947:Glucose