Serizawa Yasuhiro, Oshima Rieko, Yoshida Mitsuki, Sakon Ichika, Kitani Kazuto, Goto Ayumi, Tsuda Satoshi, Hayashi Tatsuya
Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
Biochem Biophys Res Commun. 2014 Oct 10;453(1):81-5. doi: 10.1016/j.bbrc.2014.09.066. Epub 2014 Sep 23.
Salicylate (SAL) has been recently implicated in the antidiabetic effect in humans. We assessed whether 5'-AMP-activated protein kinase (AMPK) in skeletal muscle is involved in the effect of SAL on glucose homeostasis. Rat fast-twitch epitrochlearis and slow-twitch soleus muscles were incubated in buffer containing SAL. Intracellular concentrations of SAL increased rapidly (<5 min) in both skeletal muscles, and the Thr(172) phosphorylation of the α subunit of AMPK increased in a dose- and time-dependent manner. SAL increased both AMPKα1 and AMPKα2 activities. These increases in enzyme activity were accompanied by an increase in the activity of 3-O-methyl-D-glucose transport, and decreases in ATP, phosphocreatine, and glycogen contents. SAL did not change the phosphorylation of insulin receptor signaling including insulin receptor substrate 1, Akt, and p70 ribosomal protein S6 kinase. These results suggest that SAL may be transported into skeletal muscle and may stimulate AMPK and glucose transport via energy deprivation in multiple muscle types. Skeletal muscle AMPK might be part of the mechanism responsible for the metabolic improvement induced by SAL.
近期研究表明，水杨酸盐（SAL）对人体具有抗糖尿病作用。我们评估了骨骼肌中的5'-AMP激活蛋白激酶（AMPK）是否参与SAL对葡萄糖稳态的影响。将大鼠的快肌肱三头肌和慢肌比目鱼肌置于含有SAL的缓冲液中孵育。两种骨骼肌中SAL的细胞内浓度均迅速升高（<5分钟），且AMPKα亚基的Thr(172)磷酸化呈剂量和时间依赖性增加。SAL增加了AMPKα1和AMPKα2的活性。这些酶活性的增加伴随着3-O-甲基-D-葡萄糖转运活性的增加，以及ATP、磷酸肌酸和糖原含量的降低。SAL并未改变胰岛素受体信号通路的磷酸化，包括胰岛素受体底物1、Akt和p70核糖体蛋白S6激酶。这些结果表明，SAL可能被转运到骨骼肌中，并可能通过多种肌肉类型的能量剥夺来刺激AMPK和葡萄糖转运。骨骼肌AMPK可能是SAL诱导代谢改善机制的一部分。
