title: Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
abstract: OBJECTIVE
  To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene maslinic acid (MA) exerts anti-diabetic effects.
  
  
  METHODS
  HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD).
  
  
  RESULTS
  The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content.
  
  
  CONCLUSIONS
  The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.
authors.affiliation: State Key Laboratory of Natural Medicines, National Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines, National Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, National Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Yu-Peng
authors.initials: YP
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Natural Medicines, National Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Natural Medicines, National Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.affiliation: Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, P.R. China. Electronic address: hbsun2000@yahoo.com.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural Medicines, National Drug Screening Center, China Pharmaceutical University, Nanjing 210009, China. Electronic address: lyonzhang@163.com.
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000008:administration & dosage*; D009828:Oleanolic Acid / Q000031:analogs & derivatives
chemical_list: D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; D006003:Glycogen; D024981:Glycogen Phosphorylase; D007328:Insulin; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid
keywords: Glycogen metabolism; Glycogen phosphorylation a; Insulin signal transduction; Maslinic acid