title: Sesquiterpenes from Baizhu Stimulate Glucose Uptake by Activating AMPK and PI3K.
abstract: Baizhu, the dried rhizome of Atractylodes Macrocephala Koidz (Compositae), is one of the most important traditional Chinese herbal medicines. Baizhu is generally used to treat digestive disorders and diabetes in Asian countries. This study investigates the activity of two sesquiterpenes isolated from Baizhu, atractylenolide I (AT-I) and atractylenolide II (AT-II), for their effects on glucose uptake in mouse skeletal muscle C2C12 cells, and the corresponding mechanism. These compounds show a significant stimulatory effect on glucose uptake in C2C12 myotubes. Both AT-I and AT-II significantly increased GLUT4 but not GLUT1 protein levels, and promoted GLUT4 translocation to the plasma membrane. The increased glucose uptake induced by these compounds is associated with activation of AMP-activated protein kinase (AMPK) and PI3K/Akt pathways in these cells. Further studies have indicated that AT-I and AT-II ameliorate TNF-[Formula: see text]-induced insulin resistance in C2C12 myotubes. In summary, our findings highlight the insulin mimetic activity of Baizhu in myotubes, and provide insights into the action mechanism underlying these effects. Our findings may also prove highly relevant to the development of novel therapeutic applications for these compounds.
authors.affiliation: * Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chien-Liang
authors.initials: CL
authors.lastname: Chao
authors.affiliation: § Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 404, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Huang
authors.affiliation: † School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Hang-Ching
authors.initials: HC
authors.lastname: Lin
authors.affiliation: * Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.|‡ Department of Biochemistry, National Defense Medical Center, Taipei 114, Taiwan.|¶ Department of Biotechnology, Asia University, Taichung, Taiwan.|∥ China Medical University Hospital, China Medical University, Taichung 402, Taiwan.
authors.forename: Tsu-Chung
authors.initials: TC
authors.lastname: Chang
authors.affiliation: * Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.|† School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Wen-Liang
authors.initials: WL
authors.lastname: Chang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D031174:Atractylodes / Q000737:chemistry*; D001692:Biological Transport / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007783:Lactones; D012717:Sesquiterpenes; C424804:atractylenolide I; C458582:atractylenolide II; D019869:Phosphatidylinositol 3-Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMP-activated Protein Kinase; Baizhu; C2C12 Myotubes; GLUT4; PI3K; Sesquiterpenes