Alkhateeb Hakam Hasan, Kaplan Nasser Mohammed, Al-Duais Mohammed
Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, Irbid, Jordan.
Department of Pathology and Microbiology, Jordan University of Science and Technology, Irbid, Jordan.
Rep Biochem Mol Biol. 2022 Apr;11(1):146-156. doi: 10.52547/rbmb.11.1.146.
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 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.
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.
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.
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.
橄榄果实和叶子的主要成分橄榄苦苷已被报道具有预防胰岛素抵抗和糖尿病的作用。虽然许多实验研究探讨了橄榄苦苷改善胰岛素抵抗和糖尿病的机制，但其中大部分研究是在肌肉细胞系或模型中进行的，这两种情况都有许多缺点。因此，为了简化对橄榄苦苷调节特定细胞过程机制的识别，在本研究中，我们采用分离的肌肉制剂，其能够更好地控制代谢环境并允许进行更详细的分析。
为此，将比目鱼肌在不存在或存在棕榈酸（1.5 mM）的情况下，在不存在或存在橄榄苦苷（1.5 mM）和化合物C的情况下孵育12小时。检测胰岛素刺激的葡萄糖转运、4型葡萄糖转运蛋白（GLUT4）易位、160 kDa的Akt底物（AS160）磷酸化和腺苷单磷酸激活蛋白激酶（AMPK）磷酸化。
棕榈酸处理降低了胰岛素刺激的葡萄糖转运、GLUT4易位和AS160磷酸化，但AMPK磷酸化未改变。给予橄榄苦苷（12小时）可完全恢复胰岛素刺激的葡萄糖转运，但部分恢复GLUT4易位。然而，它完全恢复了AS160磷酸化，这增加了橄榄苦苷也可能通过增加GLUT4内在活性促进葡萄糖转运恢复的可能性。用化合物C（50 μM）抑制AMPK磷酸化可阻止橄榄苦苷诱导的胰岛素刺激的葡萄糖转运、GLUT4易位和AS160磷酸化的改善。
我们的结果清楚地表明，橄榄苦苷减轻棕榈酸诱导的胰岛素抵抗似乎是通过一种依赖AMPK的机制发生的，该机制涉及AS160 - GLUT4信号系统功能的改善。
