{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:36:38Z","timestamp":1791329798873,"version":"4.3.1"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T00:00:00Z","timestamp":1370995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Quercetin is a natural polyphenolic flavonoid that displays anti\u2010diabetic properties <jats:italic>in vivo<\/jats:italic>. Its mechanism of action on insulin\u2010secreting beta cells is poorly documented. In this work, we have analysed the effects of quercetin both on insulin secretion and on the intracellular calcium concentration ([<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>]<jats:sub>i<\/jats:sub>) in beta cells, in the absence of any co\u2010stimulating factor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Experiments were performed on both <jats:styled-content style=\"fixed-case\">INS<\/jats:styled-content>\u20101 cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous time\u2010resolved fluorescence method. Variations in [<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>]<jats:sub>i<\/jats:sub> were measured using the ratiometric fluorescent <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> indicator <jats:styled-content style=\"fixed-case\">F<\/jats:styled-content>ura\u20102. <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> channel currents were recorded with the whole\u2010cell patch\u2010clamp technique.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Quercetin concentration\u2010dependently increased insulin secretion and elevated [<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>]<jats:sub>i<\/jats:sub>. These effects were not modified by the <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content> inhibitor thapsigargin (1\u2009\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup>), but were nearly abolished by the L\u2010type <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> channel antagonist nifedipine (1\u2009\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup>). Similar to the L\u2010type <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> channel agonist <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>ay <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> 8644, quercetin enhanced the L\u2010type <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> current by shifting its voltage\u2010dependent activation towards negative potentials, leading to the increase in [<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>]<jats:sub>i<\/jats:sub> and insulin secretion. The effects of quercetin were not inhibited in the presence of a maximally active concentration of <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>ay <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> 8644 (1\u2009\u03bcmol\u00b7L<jats:sup>\u22121<\/jats:sup>), with the two drugs having cumulative effects on [<jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content>]<jats:sub>i<\/jats:sub>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Taken together, our results show that quercetin stimulates insulin secretion by increasing <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> influx through an interaction with L\u2010type <jats:styled-content style=\"fixed-case\"><jats:roman>Ca<jats:sup>2+<\/jats:sup><\/jats:roman><\/jats:styled-content> channels at a site different from that of <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>ay <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content> 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12194","type":"journal-article","created":{"date-parts":[[2013,3,27]],"date-time":"2013-03-27T10:35:31Z","timestamp":1364380531000},"page":"1102-1113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["Quercetin induces insulin secretion by direct activation of L\u2010type calcium channels in pancreatic beta cells"],"prefix":"10.1111","volume":"169","author":[{"given":"G","family":"Bardy","sequence":"first","affiliation":[{"name":"D\u00e9partement de Pharmacologie M\u00e9dicale et Toxicologie H\u00f4pital Lapeyronie CHRU de Montpellier  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Virsolvy","sequence":"additional","affiliation":[{"name":"INSERM U1046 Universit\u00e9s Montpellier 1 et 2  Montpellier 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