Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4
Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4
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DOI：
10.3164/jcbn.16-120
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发表时间：
2017-11-01
影响因子：
2.4
通讯作者：
Aoki, Yoshinori
中科院分区：
文献类型：
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作者：
Fujiwara, Yoko;Tsukahara, Chisato;Aoki, Yoshinori
随着地中海饮食对人体健康的有益影响得到充分证实，橄榄油中的酚类化合物已引起人们的兴趣。橄榄苦苷是橄榄中的一种主要酚类化合物，已知可以降低四氧嘧啶诱导的糖尿病大鼠和家兔的血糖水平，然而，它对肥胖引起的2型糖尿病的作用尚不清楚。本研究旨在阐明橄榄苦苷对2型糖尿病脂毒性下骨骼肌糖耐量的影响。橄榄苦苷在没有胰岛素的C2C12细胞中增强葡萄糖摄取。单磷酸腺苷活化蛋白激酶（AMPK）可促进葡萄糖转运蛋白4 （GLUT4）向细胞膜的易位，而蛋白激酶B （Akt）则不能。橄榄苦苷生理浓度（10 pM）足以表达对C2C12细胞的有益作用。橄榄苦苷可预防棕榈酸诱导的心肌细胞胰岛素抵抗。此外，在高脂饮食小鼠腓肠肌中，橄榄苦苷也诱导GLUT4定位到细胞膜。这些结果表明橄榄苦苷可能通过降低骨骼肌的胰岛素抵抗而对2型糖尿病有效。
As the beneficial effects of the Mediterranean diet on human health are well established, the phenolic compounds in olive oil have been gaining interest. Oleuropein, a major phenolic compound in olives, is known to reduce the blood glucose levels in alloxan-induced diabetic rats and rabbits, however, its effect on type 2 diabetes caused by obesity is not clear. The purpose of this study is clarifying the effect of oleuropein on the glucose tolerance in skeletal muscle under the condition of lipotoxicity caused by type 2 diabetes. Oleuropein enhanced glucose uptake in C2C12 cells without insulin. Translocation of glucose transporter 4 (GLUT4) into the cell membrane was promoted by activation of adenosine monophosphate-activated protein kinase (AMPK) but not protein kinase B (Akt). Physiological concentration of oleuropein (10 pM) was sufficient to express beneficial effects on C2C12 cells. Oleuropein prevented palmitic acid-induced myocellular insulin resistance. Furthermore, in gastrocnemius muscles of mice fed a high fat diet, oleuropein also induced the GLUT4 localization into cell membrane. These results suggest the possibility of oleuropein to be effective for type 2 diabetes by reducing insulin resistance in skeletal muscles.