title: Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Département de Pharmacologie Médicale et Toxicologie, Hôpital Lapeyronie, CHRU de Montpellier, Montpellier, France.
authors.forename: G
authors.initials: G
authors.lastname: Bardy
authors.forename: A
authors.initials: A
authors.lastname: Virsolvy
authors.forename: J F
authors.initials: JF
authors.lastname: Quignard
authors.forename: M A
authors.initials: MA
authors.lastname: Ravier
authors.forename: G
authors.initials: G
authors.lastname: Bertrand
authors.forename: S
authors.initials: S
authors.lastname: Dalle
authors.forename: G
authors.initials: G
authors.lastname: Cros
authors.forename: R
authors.initials: R
authors.lastname: Magous
authors.forename: S
authors.initials: S
authors.lastname: Richard
authors.forename: C
authors.initials: C
authors.lastname: Oiry
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007328:Insulin; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D011794:Quercetin; D009543:Nifedipine; D002118:Calcium