Antidiabetic effect of gomisin N via activation of AMP-activated protein kinase.
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.
['Jung|Dae Young|DY|', 'Kim|Ji-Hyun|JH|', 'Lee|Hoyoung|H|', 'Jung|Myeong Ho|MH|']
D055372:AMP-Activated Protein Kinases D000818:Animals D001786:Blood Glucose D034242:Cyclooctanes D003920:Diabetes Mellitus D004305:Dose-Response Relationship, Drug D004789:Enzyme Activation D005260:Female D007004:Hypoglycemic Agents D007328:Insulin D007333:Insulin Resistance D017705:Lignans D051379:Mice D008810:Mice, Inbred C57BL D008931:Mitochondria, Muscle D018482:Muscle, Skeletal D001678:Organelle Biogenesis D011083:Polycyclic Compounds
Antidiabetes Gomisin N AMP-Activated protein kinase Glucose transporter 4 Mitochondria biogenesis Fatty acid oxidation