Insulin secretion preservation is a major issue for the prevention or treatment of type 2 diabetes. We previously showed on b-cells that quercetin (Q), but not resve- ratrol (R) or N-acetyl cysteine (NAC), amplified glucose-induced insulin secretion in a calcium- and ERK1/2-dependent manner. Quercetin, but not resveratrol or NAC, also protected b-cell function and hyperamplified ERK1/2 phosphorylation in oxidative stress conditions. As quercetin may interfere with other stress-activated protein kinases (JNK and p38 MAPK), we further explored MAPK cross talks and their relationships with the mechanism of the protective effect of quercetin against oxidative stress. In INS-1 insulin-secreting b-cells, using pharmacological inhibitors of MAPK pathways, we found that under oxidative stress (50 lM H2O2) and glu- cose-stimulating insulin secretion conditions: (i) p38 MAPK phosphorylation was increased and regulated by ERK1/2 (positively) and JNK (negatively), although p38 MAPK activation did not seem to play any significant role in oxidative stress- induced insulin secretion impairment; (ii) the JNK pathway appeared to inhibit both ERK1/2 activation and insulin secretion, although JNK phosphorylation was not significantly changed in our experimental conditions; (iii) the functionality of b-cell in the presence of oxidative stress was closely linked to the level of ERK1/2 activation, (iv) quercetin, resveratrol, or NAC inhibited H2O2-induced p38 MAPK phosphorylation. The preservation of b-cell function against oxidative stress appears dependent on the balance between ERK1/2 and JNK activation. The pro- tecting effect of quercetin appears due to ERK1/2 hyperactivation, possibly induced by L-type calcium channel opening as we recently showed

Insulin secretion, MAP kinase cross talks, oxidative stress, quercetin, b-cell