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Br J Pharmacol. 2013 Jul;169(5):1102-13. doi: 10.1111/bph.12194.

Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells.

Author information

  • 1Département de Pharmacologie Médicale et Toxicologie, Hôpital Lapeyronie, CHRU de Montpellier, Montpellier, France.

Abstract

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 ([Ca(2+)]i) in beta cells, in the absence of any co-stimulating factor.

EXPERIMENTAL APPROACH:

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 [Ca(2+)]i were measured using the ratiometric fluorescent Ca(2+) indicator Fura-2. Ca(2+) channel currents were recorded with the whole-cell patch-clamp technique.

KEY RESULTS:

Quercetin concentration-dependently increased insulin secretion and elevated [Ca(2+)]i. These effects were not modified by the SERCA inhibitor thapsigargin (1 μmol·L(-1)), but were nearly abolished by the L-type Ca(2+) channel antagonist nifedipine (1 μmol·L(-1)). Similar to the L-type Ca(2+) channel agonist Bay K 8644, quercetin enhanced the L-type Ca(2+) current by shifting its voltage-dependent activation towards negative potentials, leading to the increase in [Ca(2+)]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 [Ca(2+)]i.

CONCLUSIONS AND IMPLICATIONS:

Taken together, our results show that quercetin stimulates insulin secretion by increasing Ca(2+) influx through an interaction with L-type Ca(2+) 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.

© 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

PMID:
23530660
[PubMed - in process]
PMCID:
PMC3696332
Free PMC Article

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