Jung Dae Young, Kim Ji-Hyun, Lee Hoyoung, Jung Myeong Ho
Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea; Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan 50612, Republic of Korea.
KM Fundamental Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Biochem Biophys Res Commun. 2017 Dec 16;494(3-4):587-593. doi: 10.1016/j.bbrc.2017.10.120. Epub 2017 Oct 25.
Gomisin N (GN) is a lignan derived from Schisandra chinensis. AMP-activated kinase (AMPK) has gained attention as a therapeutic target for the treatment of metabolic syndrome. Previously, we reported that GN activated the AMPK pathway and ameliorated high-fat diet (HFD)-induced hepatic steatosis. In this study, we investigated the anti-diabetic effects of GN in C2C12 myotubes and HFD obese mice. GN enhanced the phosphorylation of AMPK/acetyl-CoA carboxylase (ACC) and Akt. In addition, GN promoted glucose uptake in C2C12 myotubes, which was accompanied by the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Treatment with compound C, an AMPK inhibitor, suppressed GN-mediated stimulation of glucose uptake. Furthermore, GN increased the expression of mitochondria biogenesis and fatty acid oxidation genes in C2C12 myotubes. In the in vivo study, administration of GN to HFD mice decreased the levels of fasting blood glucose and insulin, and improved glucose tolerance in HFD obese mice. GN administration rescued the decreased phosphorylation of AMPK and Akt and stimulated the expression of mitochondria biogenesis genes in the skeletal muscle of HFD mice. These findings suggested that GN exerted anti-hyperglycemic effects through AMPK activation.
戈米辛N（GN）是一种从五味子中提取的木脂素。AMP激活蛋白激酶（AMPK）作为治疗代谢综合征的靶点已受到关注。此前，我们报道GN可激活AMPK信号通路并改善高脂饮食（HFD）诱导的肝脂肪变性。在本研究中，我们研究了GN对C2C12肌管和HFD肥胖小鼠的抗糖尿病作用。GN增强了AMPK/乙酰辅酶A羧化酶（ACC）和Akt的磷酸化。此外，GN促进C2C12肌管对葡萄糖的摄取，这伴随着葡萄糖转运蛋白4（GLUT4）向质膜的转位。用AMPK抑制剂化合物C处理可抑制GN介导的葡萄糖摄取刺激。此外，GN增加了C2C12肌管中线粒体生物发生和脂肪酸氧化基因的表达。在体内研究中，给HFD小鼠施用GN可降低空腹血糖和胰岛素水平，并改善HFD肥胖小鼠的葡萄糖耐量。给HFD小鼠施用GN可挽救AMPK和Akt磷酸化的降低，并刺激HFD小鼠骨骼肌中线粒体生物发生基因的表达。这些发现表明GN通过激活AMPK发挥抗高血糖作用。
