title: AMPK, a metabolic sensor, is involved in isoeugenol-induced glucose uptake in muscle cells.
abstract: Isoeugenol exerts various beneficial effects on human health. However, the mechanisms underlying these effects are poorly understood. In this study, we observed that isoeugenol activated AMP-activated protein kinase (AMPK) and increased glucose uptake in rat L6 myotubes. Isoeugenol-induced increase in intracellular calcium concentration and glucose uptake was inhibited by STO-609, an inhibitor of calcium/calmodulin-dependent protein kinase kinase (CaMKK). Isoeugenol also increased the phosphorylation of protein kinase C-α (PKCα). Chelation of calcium with BAPTA-AM blocked isoeugenol-induced AMPK phosphorylation and glucose uptake. Isoeugenol stimulated p38MAPK phosphorylation that was inhibited after pretreatment with compound C, an AMPK inhibitor. Isoeugenol also increased glucose transporter type 4 (GLUT4) expression and its translocation to the plasma membrane. GLUT4 translocation was not observed after the inhibition of AMPK and CaMKK. In addition, isoeugenol activated the Akt substrate 160 (AS160) pathway, which is downstream of the p38MAPK pathway. Knockdown of the gene encoding AS160 inhibited isoeugenol-induced glucose uptake. Together, these results indicate that isoeugenol exerts beneficial health effects by activating the AMPK/p38MAPK/AS160 pathways in skeletal muscle.
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Nami
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Jung Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Hyung Ip
authors.initials: HI
authors.lastname: Kim
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Chul Su
authors.initials: CS
authors.lastname: Lee
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Ryoo
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea.
authors.forename: Geum-Sook
authors.initials: GS
authors.lastname: Hwang
authors.affiliation: Department of AnatomyKorea University College of Medicine, Seoul 136-701, South KoreaDepartment of MedicineKorea University College of Medicine, Seoul, South KoreaIntegrated Metabolomics Research GroupKorea Basic Science Institute (KBSI), Western Seoul Center, Seoul, South KoreaDepartment of Life ScienceEwha Womans University, Seoul, South Korea anatomykim@korea.ac.kr.
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Kim
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005054:Eugenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D034741:RNA, Small Interfering; D005054:Eugenol; C036643:isoeugenol; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D002118:Calcium
keywords: AMPK; glucose uptake; isoeugenol; p38 MAPK