title: Modulation of glucose metabolism by a natural compound from Chloranthus japonicus via activation of AMP-activated protein kinase.
abstract: AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose metabolism. Here, we demonstrated that shizukaol F, a natural compound isolated from Chloranthus japonicus, can activate AMPK and modulate glucose metabolism both in vitro and in vivo. Shizukaol F increased glucose uptake in differentiated C2C12 myotubes by stimulating glucose transporter-4 (GLUT-4) membraned translocation. Treatment of primary mouse hepatocytes with shizukaol F decreased the expression of phosphoenolpyruvate carboxykinase 2 (PEPCK), glucose-6-phosphatase (G6Pase) and suppressed hepatic gluconeogenesis. Meanwhile, a single oral dose of shizukaol F reduced gluconeogenesis in C57BL/6 J mice. Further studies indicated that shizukaol F modulates glucose metabolism mainly by AMPKa phosphorylation activity. In addition, we also found that shizukaol F depolarizes the mitochondrial membrane and inhibits respiratory complex I, which may result in AMPK activation. Our results highlight the potential value of shizukaol F as a possible treatment of metabolic syndrome.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, 230027, China.|Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.|Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Rongkuan
authors.initials: R
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Fei
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. haiyangliu@mail.kib.ac.cn.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science & Technology of China, Hefei, 230027, China. wujr@sibs.ac.cn.|Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. wujr@sibs.ac.cn.|School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. wujr@sibs.ac.cn.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Wu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology; D064028:Tracheophyta / Q000737:chemistry*
chemical_list: D001688:Biological Products; D010936:Plant Extracts; D012717:Sesquiterpenes; C583587:shizukaol F; D055372:AMP-Activated Protein Kinases; D005947:Glucose