Quercetin induces insulin secretion by direct activation of L-type calcium channels in pancreatic beta cells.
Br J Pharmacol
; 169(5): 1102-13, 2013 Jul.
Article
en En
| MEDLINE
| ID: mdl-23530660
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. EXPERIMENTALAPPROACH:
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. KEYRESULTS:
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Quercetina
/
Agonistas de los Canales de Calcio
/
Canales de Calcio Tipo L
/
Células Secretoras de Insulina
Límite:
Animals
Idioma:
En
Revista:
Br J Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Francia