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

Abstract

BACKGROUND AND PURPOSEQuercetin 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 APPROACHExperiments 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 RESULTSQuercetin concentration-dependently increased insulin secretion and elevated [Ca 2+ ]i. These effects were not modified by the SERCA inhibitor thapsigargin (1 mmol·L CONCLUSIONS AND IMPLICATIONSTaken 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. AbbreviationsBay

Changes of intracellular Ca<sup>2+</sup> in quercetin-induced autophagy progression

“…Quercetin caused significant depletion of cytosolic calcium levels and decreased calcium uptake from the intracellular stores in MDA MB 231 cells [24]. Quercetin could stimulate insulin secretion by increasing Ca 2+ influx through an interaction with L-type Ca 2+ channels [25]. Natsume et al [26] reported that quercetin suppressed the ER stress caused by calcium dynamics dysregulation by the inhibition of PI3K.…”

Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells

“…Quercetin interacts with L-type Cav1 in a different site from that of the agonist Bay K 8644 (1,phenyl]-3-pyridinecarboxylic acid, methyl ester). The mechanism acts by shifting the voltage-dependent activation toward negative potentials (Bardy et al, 2013). L-type Cav1 channels are the major contributors to the whole cell Cav current and insulin granule exocytosis in human, rat, and mouse beta cells.…”

Quercetin Inhibits Pacemaker Potentials via Nitric Oxide/cGMP-Dependent Activation and TRPM7/ANO1 Channels in Cultured Interstitial Cells of Cajal from Mouse Small Intestine

“…Quercetin has a variety of activities in man. For example, it has been reported to have antioxidant [5][6][7], anti-inflammatory [8], anti-anaphylactic [9], anti-aging [10], antiplatelet aggregatory [11], radioprotective [12], immunomodulatory [13], antidiabetic [14], and anticancer [15] effects, and to improve lipid metabolism [16,17] and endurance exercise capacity [18]. Quercetin also reduces gastrointestinal (GI) intestinal transit in mice [19], induces intestinal smooth muscle relaxation [20], and prevents castor oil-induced diarrhea [21].…”