title: Glabridin induces glucose uptake via the AMP-activated protein kinase pathway in muscle cells.
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 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 15 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.
authors: Department of Agrobioscience, Graduate School of Agricultural Science, Nada-ku, Kobe University, Kobe 657-8501, Japan.
authors: Keisuke
authors: K
authors: Sawada
authors: Department of Agrobioscience, Graduate School of Agricultural Science, Nada-ku, Kobe University, Kobe 657-8501, Japan.
authors: Yoko
authors: Y
authors: Yamashita
authors: Department of Agrobioscience, Graduate School of Agricultural Science, Nada-ku, Kobe University, Kobe 657-8501, Japan.
authors: Tianshun
authors: T
authors: Zhang
authors: QOL Division, Kaneka Corporation, Kita-ku, Osaka 530-8288, Japan.
authors: Kaku
authors: K
authors: Nakagawa
authors: Department of Agrobioscience, Graduate School of Agricultural Science, Nada-ku, Kobe University, Kobe 657-8501, Japan. Electronic address: ashida@kobe-u.ac.jp.
authors: Hitoshi
authors: H
authors: Ashida
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007529:Isoflavones; D010636:Phenols; D055372:AMP-Activated Protein Kinases; C107601:glabridin; D005947:Glucose
keywords: Adenosine monophosphate-activated protein kinase; Glabridin; Glucose transporter type 4; Glucose uptake; Muscle cells