Quercetin potentiates insulin secretion and protects INS‐1 pancreatic β‐cells against oxidative damage via the ERK1/2 pathway

BACKGROUND AND PURPOSE Quercetin lowers plasma glucose, normalizes glucose tolerance tests and preserves pancreatic β‐cell integrity in diabetic rats. However, its mechanism of action has never been explored in insulin‐secreting β‐cells. Using the INS‐1 β‐cell line, the effects of quercetin were determined on glucose‐ or glibenclamide‐induced insulin secretion and on β‐cell dysfunctions induced by hydrogen peroxide (H 2 O 2 ). 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 APPROACH Insulin 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 RESULTS Quercetin (20 µmol·L −1 ) potentiated both glucose (8.3 mmol·L −1 )‐ and glibenclamide (0.01 µmol·L −1 )‐induced insulin secretion and ERK1/2 phosphorylation. The ERK1/2 (but not the protein kinase A) signalling pathway played a crucial role in the potentiation of glucose‐induced insulin secretion by quercetin. In addition, quercetin (20 µmol·L −1 ), protected β‐cell function and viability against oxidative damage induced by 50 µmol·L −1 H 2 O 2 and induced a major phosphorylation of ERK1/2. In the same conditions, resveratrol or NAC were ineffective. CONCLUSION AND IMPLICATIONS Quercetin potentiated glucose and glibenclamide‐induced insulin secretion and protected β‐cells against oxidative damage. Our study suggested that ERK1/2 played a major role in those effects. The potential of quercetin in preventing β‐cell dysfunction associated with diabetes deserves further investigation.