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Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cells

Sawada, Keisuke, Yamashita, Yoko, Zhang, Tianshun, Nakagawa, Kaku, Ashida, Hitoshi
Molecular and Cellular Endocrinology 2014 v.393 pp. 99-108
AMP-activated protein kinase, diabetes, dose response, glucose, glucose transporters, glycogen, hyperglycemia, isoflavones, lactic acid, licorice, metabolism, mice, myotubes, phosphatidylinositol 3-kinase, phosphorylation, plasma membrane, skeletal muscle, small interfering RNA, therapeutics
The present study demonstrates that glabridin, a prenylated isoflavone in licorice, stimulates glucose uptake through the adenosine monophosphate-activated protein kinase (AMPK) pathway in L6 myotubes. Treatment with glabridin for 4h induced glucose uptake in a dose-dependent manner accompanied by the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. Glabridin needed at least 4h to increase glucose uptake, while it significantly decreased glycogen and increased lactic acid within 15min. Pharmacological inhibition of AMPK by Compound C suppressed the glabridin-induced glucose uptake, whereas phosphoinositide 3-kinase and Akt inhibition by LY294002 and Akt1/2 inhibitor, respectively, did not. Furthermore, glabridin induced AMPK phosphorylation, and siRNA for AMPK completely abolished glabridin-induced glucose uptake. We confirmed that glabridin-rich licorice extract prevent glucose intolerance accompanied by the AMPK-dependent GLUT4 translocation in the plasma membrane of mice skeletal muscle. These results indicate that glabridin may possess a therapeutic effect on metabolic disorders, such as diabetes and hyperglycemia, by modulating glucose metabolism through AMPK in skeletal muscle cells.