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Quercetin induces insulin secretion by direct activation of L‐type calcium channels in pancreatic beta cells
Author(s) -
Bardy G,
Virsolvy A,
Quignard J F,
Ravier M A,
Bertrand G,
Dalle S,
Cros G,
Magous R,
Richard S,
Oiry C
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12194
Subject(s) - thapsigargin , quercetin , nifedipine , medicine , endocrinology , insulin , calcium channel , pancreatic islets , secretion , voltage dependent calcium channel , chemistry , serca , l type calcium channel , calcium , beta cell , agonist , biophysics , biology , islet , biochemistry , receptor , atpase , enzyme , antioxidant
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 F ura‐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 B ay 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 B ay 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 B ay K 8644. These data contribute to a better understanding of quercetin's mechanism of action on insulin secretion.