Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada.
Centre for Bone and Muscle Health, Brock University, St Catharines, ON L2S 3A1, Canada.
Nutrients. 2018 Nov 2;10(11):1623. doi: 10.3390/nu10111623.
Elevated blood free fatty acids (FFAs), as seen in obesity, impair muscle insulin action leading to insulin resistance and Type 2 diabetes mellitus. Serine phosphorylation of the insulin receptor substrate (IRS) is linked to insulin resistance and a number of serine/threonine kinases including JNK, mTOR and p70 S6K have been implicated in this process. Activation of the energy sensor AMP-activated protein kinase (AMPK) increases muscle glucose uptake, and in recent years AMPK has been viewed as an important target to counteract insulin resistance. We reported recently that rosemary extract (RE) increased muscle cell glucose uptake and activated AMPK. However, the effect of RE on FFA-induced muscle insulin resistance has never been examined. In the current study, we investigated the effect of RE in palmitate-induced insulin resistant L6 myotubes. Exposure of myotubes to palmitate reduced the insulin-stimulated glucose uptake, increased serine phosphorylation of IRS-1, and decreased the insulin-stimulated phosphorylation of Akt. Importantly, exposure to RE abolished these effects and the insulin-stimulated glucose uptake was restored. Treatment with palmitate increased the phosphorylation/activation of JNK, mTOR and p70 S6K whereas RE completely abolished these effects. RE increased the phosphorylation of AMPK even in the presence of palmitate. Our data indicate that rosemary extract has the potential to counteract the palmitate-induced muscle cell insulin resistance and further studies are required to explore its antidiabetic properties.
血液中游离脂肪酸（FFAs）水平升高，如肥胖症患者所见，会损害肌肉胰岛素作用，导致胰岛素抵抗和 2 型糖尿病。胰岛素受体底物（IRS）的丝氨酸磷酸化与胰岛素抵抗有关，包括 JNK、mTOR 和 p70 S6K 在内的许多丝氨酸/苏氨酸激酶都与这一过程有关。能量感受器 AMP 激活蛋白激酶（AMPK）的激活可增加肌肉葡萄糖摄取，近年来，AMPK 被视为对抗胰岛素抵抗的重要靶点。我们最近报道称，迷迭香提取物（RE）可增加肌肉细胞的葡萄糖摄取并激活 AMPK。然而，RE 对 FFA 诱导的肌肉胰岛素抵抗的影响从未被研究过。在本研究中，我们研究了 RE 对棕榈酸诱导的胰岛素抵抗 L6 肌管的影响。肌管暴露于棕榈酸会降低胰岛素刺激的葡萄糖摄取，增加 IRS-1 的丝氨酸磷酸化，并降低胰岛素刺激的 Akt 磷酸化。重要的是，暴露于 RE 可消除这些作用，并恢复胰岛素刺激的葡萄糖摄取。棕榈酸处理会增加 JNK、mTOR 和 p70 S6K 的磷酸化/激活，而 RE 则完全消除了这些作用。RE 甚至在存在棕榈酸的情况下也能增加 AMPK 的磷酸化。我们的数据表明，迷迭香提取物具有抵抗棕榈酸诱导的肌肉细胞胰岛素抵抗的潜力，需要进一步研究来探索其抗糖尿病特性。
