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.

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1 Experiments were designed to determine in two arteries (the guinea-pig carotid and the porcine coronary arteries) whether or not the endothelium-derived hyperpolarizing factor (EDHF) can be identi®ed as potassium ions, and to determine whether or not the inwardly rectifying potassium current and the Na 3 In vascular smooth muscle cells of guinea-pig carotid and porcine coronary arteries, acetylcholine and bradykinin induced endothelium-dependent hyperpolarizations (718+1 mV, n=39 and 719+1 mV, n=7, respectively). The hyperpolarizations were not aected signi®cantly by ouabain (1 mM), barium chloride (up to 100 mM) or the combination of ouabain plus barium. 4 In both arteries, increasing extracellular potassium concentration by 5 or 10 mM induced either depolarization or in a very few cases small hyperpolarizations which never exceeded 2 mV. 5 In isolated smooth muscle cells of the guinea-pig carotid artery, patch-clamp experiments shows that only 20% of the vascular smooth muscle cells expressed inwardly rectifying potassium channels. The current density recorded was low (0.5+0.1 pA pF 71 , n=8). 6 These results indicate that, in two dierent vascular preparations, barium sensitive-inwardly rectifying potassium conductance and the ouabain sensitive-Na + /K + pump are not involved in the EDHF-mediated hyperpolarization. Furthermore, potassium did not mimic the eect of EDHF pointing out that potassium and EDHF are not the same entity in those arteries.