<scp>MAP</scp> Kinase cross talks in oxidative stress‐induced impairment of insulin secretion. Involvement in the protective activity of quercetin

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Résumé

Insulin secretion preservation is a major issue for the prevention or treatment of type 2 diabetes. We previously showed on β-cells that quercetin (Q), but not resveratrol (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 β-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 β-cells, using pharmacological inhibitors of MAPK pathways, we found that under oxidative stress (50 μm H2O2) and glucose-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 β-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 β-cell function against oxidative stress appears dependent on the balance between ERK1/2 and JNK activation. The protecting effect of quercetin appears due to ERK1/2 hyperactivation, possibly induced by L-type calcium channel opening as we recently showed.

Mots-clés

Oxidative stress, p38 mitogen-activated protein kinases, MAPK/ERK pathway, Phosphorylation, Kinase, Resveratrol, Secretion, Insulin, Protein kinase A, Chemistry, Internal medicine, Endocrinology, Biology, Cell biology, Biochemistry, Medicine