Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8477158 | Molecular and Cellular Endocrinology | 2014 | 10 Pages |
Abstract
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 4Â h 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 4Â h to increase glucose uptake, while it significantly decreased glycogen and increased lactic acid within 15Â min. 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.
Keywords
LKB1TGF-β-activated kinase 1UCPAS160glabridinG6PDHTAK1KRH2-DeoxyglucoseGLUT42DGCaMKIIPPARγFBSAMPKPI3KACCAICARACOFASacyl CoA oxidaseBSACa2+/calmodulin-dependent protein kinase IIbovine serum albuminacetyl coA carboxylasefatty acid synthaseGlucose uptakefetal bovine serumMuscle cellsphosphoinositide 3-kinaseGlucose transporter type 4Uncoupling proteinadenosine monophosphate-activated protein kinaseliver kinase B1glucose-6-phosphate dehydrogenaseperoxisome proliferator-activated receptor γ
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Authors
Keisuke Sawada, Yoko Yamashita, Tianshun Zhang, Kaku Nakagawa, Hitoshi Ashida,