Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice.
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.
Colsoul
Barbara
B
Laboratory of Ion Channel Research and Gene Expression Unit, Department of Molecular Cell Biology, Katholieke Universiteit Leuven, B-3001 Louvain, Belgium.
Schraenen
Anica
A
Lemaire
Katleen
K
Quintens
Roel
R
Van Lommel
Leentje
L
Segal
Andrei
A
Owsianik
Grzegorz
G
Talavera
Karel
K
Voets
Thomas
T
Margolskee
Robert F
RF
Kokrashvili
Zaza
Z
Gilon
Patrick
P
Nilius
Bernd
B
Schuit
Frans C
FC
Vennekens
Rudi
R
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
D002412:Cations; D007328:Insulin; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse; D005947:Glucose