These authors contributed equally.
Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells
Article first published online: 12 JUN 2013
© 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society
British Journal of Pharmacology
Volume 169, Issue 5, pages 1102–1113, July 2013
How to Cite
Bardy, G., Virsolvy, A., Quignard, J. F., Ravier, M. A., Bertrand, G., Dalle, S., Cros, G., Magous, R., Richard, S. and Oiry, C. (2013), Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells. British Journal of Pharmacology, 169: 1102–1113. doi: 10.1111/bph.12194
- Issue published online: 12 JUN 2013
- Article first published online: 12 JUN 2013
- Accepted manuscript online: 27 MAR 2013 05:15AM EST
- Manuscript Accepted: 21 MAR 2013
- Manuscript Revised: 1 MAR 2013
- Manuscript Received: 26 JUL 2012
- pancreatic beta cells;
- insulin secretion;
- Ca2+ influx;
- L-type Ca2+ currents
Background and Purpose
Quercetin is a natural polyphenolic flavonoid that displays anti-diabetic properties in vivo. Its mechanism of action on insulin-secreting 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 ([Ca2+]i) in beta cells, in the absence of any co-stimulating factor.
Experiments were performed on both INS-1 cell line and rat isolated pancreatic islets. Insulin release was quantified by the homogeneous time-resolved fluorescence method. Variations in [Ca2+]i were measured using the ratiometric fluorescent Ca2+ indicator Fura-2. Ca2+ channel currents were recorded with the whole-cell patch-clamp technique.
Quercetin concentration-dependently increased insulin secretion and elevated [Ca2+]i. These effects were not modified by the SERCA inhibitor thapsigargin (1 μmol·L−1), but were nearly abolished by the L-type Ca2+ channel antagonist nifedipine (1 μmol·L−1). Similar to the L-type Ca2+ channel agonist Bay K 8644, quercetin enhanced the L-type Ca2+ current by shifting its voltage-dependent activation towards negative potentials, leading to the increase in [Ca2+]i and insulin secretion. The effects of quercetin were not inhibited in the presence of a maximally active concentration of Bay K 8644 (1 μmol·L−1), with the two drugs having cumulative effects on [Ca2+]i.
Conclusions and Implications
Taken together, our results show that quercetin stimulates insulin secretion by increasing Ca2+ influx through an interaction with L-type Ca2+ channels at a site different from that of Bay K 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion.