BACKGROUND AND PURPOSEQuercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic b-cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin-secreting b-cells. Using the INS-1 b-cell line, the effects of quercetin were determined on glucose-or glibenclamide-induced insulin secretion and on b-cell dysfunctions induced by hydrogen peroxide (H2O2). These effects were analysed along with the activation of the extracellular signal-regulated kinase (ERK)1/2 pathway. N-acetyl-L-cysteine (NAC) and resveratrol, two antioxidants also known to exhibit some anti-diabetic properties, were used for comparison. EXPERIMENTAL APPROACHInsulin release was quantified by the homogeneous time resolved fluorescence method and ERK1/2 activation tested by Western blot experiments. Cell viability was estimated by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) colorimetric assay. KEY RESULTSQuercetin (20 mmol·L ), protected b-cell function and viability against oxidative damage induced by 50 mmol·L -1 H2O2 and induced a major phosphorylation of ERK1/2. In the same conditions, resveratrol or NAC were ineffective. CONCLUSION AND IMPLICATIONSQuercetin potentiated glucose and glibenclamide-induced insulin secretion and protected b-cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing b-cell dysfunction associated with diabetes deserves further investigation.

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

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