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

Colsoul, Barbara;Schraenen, Anica;Lemaire, Katleen;Quintens, Roel;Vennekens, Rudi;et.al.
(2010) Proceedings of the National academy of sciences of the United States of America — Vol. 107, n° 11, p. 5208-5213 (2010)

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Authors
  • Colsoul, Barbara
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  • Schraenen, Anica
    Author
  • Lemaire, Katleen
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  • Quintens, Roel
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  • Gilon, Patrickorcid-logoUCLouvain
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  • Vennekens, Rudi
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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.
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Colsoul, B., Schraenen, A., Lemaire, K., Quintens, R., Van Lommel, L., Segal, A., Owsianik, G., Talavera, K., Voets, T., Margolskee, R. F., Kokrashvili, Z., Gilon, P., Nilius, B., Schuit, F. C., & Vennekens, R. (2010). Loss of high-frequency glucose-induced Ca2+ oscillations in pancreatic islets correlates with impaired glucose tolerance in Trpm5-/- mice. Proceedings of the National academy of sciences of the United States of America, 107(11), 5208-5213. https://doi.org/10.1073/pnas.0913107107 (Original work published 2010)