Understanding the Mechanism Underlie the Antidiabetic Activity of Oleuropein Using Ex-Vivo Approach |
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| Authors: | Hakam Hasan Alkhateeb Nasser Mohammed Kaplan Mohammed Al-Duais |
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| Affiliation: | 1. Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan. ; 2. Department of Pathology and Microbiology, Jordan University of Science and Technology, Irbid, Jordan. ; 3. Margaret A. Gilliam Institute for Global Food Security, McGill University, Montreal, QC, Canada. |
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| Abstract: | Background:Oleuropein, the main constituent of olive fruit and leaves, has been reported to protect against insulin resistance and diabetes. While many experimental investigations have examined the mechanisms by which oleuropein improves insulin resistance and diabetes, much of these investigations have been carried out in either muscle cell lines or in vivo models two scenarios with many drawbacks. Accordingly, to simplify identification of mechanisms by which oleuropein regulates specific cellular processes, we resort, in the present study, to isolated muscle preparation which enables better metabolic milieu control and permit more detailed analyses.Methods:For this purpose, soleus muscles were incubated for 12 h without or with palmitate (1.5 mM) in the presence or absence of oleuropein (1.5 mM), and compound C. Insulin-stimulated glucose transport, glucose transporter type 4 (GLUT4) translocation, Akt substrate of 160 kDa (AS160) phosphorylation and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation were examined.Results:Palmitate treatment reduced insulin-stimulated glucose transport, GLUT4 translocation and AS160 phosphorylation, but AMPK phosphorylation was not changed. Oleuropein administration (12 h) fully rescued insulin-stimulated glucose transport, but partially restored GLUT4 translocation. However, it fully restored AS160 phosphorylation, raising the possibility that oleuropein may also have contributed to the restoration of glucose transport by increased GLUT4 intrinsic activity. Inhibition of AMPK phosphorylation with compound C (50 µM) prevented oleuropein -induced improvements in insulin-stimulated glucose transport, GLUT4 translocation, and AS160 phosphorylation.Conclusion:Our results clearly indicate that oleuropein alleviates palmitate-induced insulin resistance appears to occur via an AMPK-dependent mechanism involving improvements in the functionality of the AS160-GLUT4 signaling system.Key Words: AMPK, GLUT4, Muscle, Insulin resistance, Oleuropein |
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