Premium
MAP Kinase cross talks in oxidative stress‐induced impairment of insulin secretion. Involvement in the protective activity of quercetin
Author(s) -
Youl Estelle,
Magous Richard,
Cros Gérard,
Oiry Catherine
Publication year - 2014
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12078
Subject(s) - oxidative stress , p38 mitogen activated protein kinases , mapk/erk pathway , phosphorylation , kinase , resveratrol , secretion , insulin , protein kinase a , chemistry , medicine , endocrinology , biology , microbiology and biotechnology , biochemistry
Abstract 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 ERK 1/2‐dependent manner. Quercetin, but not resveratrol or NAC , also protected β‐cell function and hyperamplified ERK 1/2 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 μ m H 2 O 2 ) and glucose‐stimulating insulin secretion conditions: (i) p38 MAPK phosphorylation was increased and regulated by ERK 1/2 (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 ERK 1/2 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 ERK 1/2 activation, (iv) quercetin, resveratrol, or NAC inhibited H 2 O 2 ‐induced p38 MAPK phosphorylation. The preservation of β‐cell function against oxidative stress appears dependent on the balance between ERK 1/2 and JNK activation. The protecting effect of quercetin appears due to ERK 1/2 hyperactivation, possibly induced by L‐type calcium channel opening as we recently showed ( Br. J. Pharmacol . 2013, 169, 1102–1113).