Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice

Barbara Colsoul, Anica Schraenen, Katleen Lemaire, Roel Quintens, Leentje Van Lommel, Andrei Segal, Grzegorz Owsianik, Karel Talavera, Thomas Voets, Robert F. Margolskee, Zaza Kokrashvili, Patrick Gilon, Bernd Nilius, Frans C. Schuit, Rudi Vennekens, Sarah Baatout

    Research outputpeer-review


    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.
    Original languageEnglish
    Pages (from-to)5208-5213
    JournalProceedings of the National Academy of Sciences of the United States of America
    Issue number11
    StatePublished - Mar 2010

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