Oleuropein activated AMPK and induced insulin sensitivity in C2C12 muscle cells

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• 作者：Fatma Hadrich^a ; Marie Garcia^b ; Amina Maalej^a ; Marthe Moldes^b ; Hiroko Isoda^c ; ^d ; Bruno Feve^b ; Sami Sayadi^a ; ^{sami.sayadi@cbs.rnrt.tn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Skeletal muscle cells ; AMPK ; MAPK ; Insulin sensitivity ; Oleuropein
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：15 April 2016
• 年：2016
• 卷：151
• 期：Complete
• 页码：167-173
• 全文大小：633 K

文摘

Oleuropein has been recognized as an important medicinal compound because of its various biological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. Here, we evaluate the antioxidant activity as well as the mechanism of the hypoglycemic effects of oleuropein in C2C12 cells and we establish the mechanism underlying these effects.

Main methods

To perform this study, C2C12 cells viability was analyzed via MTT assay and the antioxidant activity was investigated by ROS and TBARS assays. Also, the effect of oleuropein on AMPK and PI3 kinase signaling pathways was evaluated.

Key findings

Treatment with oleuropein was able to protect cells against H₂O₂ induced stress in cells. On the other hand, the molecular bases of its actions have been scarcely understood. Oleuropein significantly enhanced glucose consumption and the phosphorylation of AMPK (AMP-activated protein kinase/ACC (acetyl-CoA carboxylase)) and MAPKs (mitogen-activated protein kinases), but not PI3 kinase (Phosphatidylinositol 3-kinase)/Akt. However, the co-treatment of oleuropein and insulin improved the insulin sensitivity via insulin-dependent (PI3 kinase/Akt) and insulin independent (AMPK/ACC) pathways. These results could be confirmed from the findings of GLUT4 translocation which was strongly enhanced in the case of oleuropein.

Significance

Our results provide important insights for the possible mechanism of action of oleuropein as a therapeutic agent in diabetic patients.