title: Pentacyclic Triterpenoids from Astilbe rivularis that Enhance Glucose Uptake via the Activation of Akt and Erk1/2 in C2C12 Myotubes.
abstract: Glucose uptake into insulin-sensitive tissues is important for the regulation of blood glucose. This study has investigated whether the pentacyclic triterpenoids substituted with a carboxylic acid at the C-27 position isolated from Astilbe rivularis can enhance glucose uptake and subsequently to also examine their underlying molecular mechanisms. The structure of the new pentacyclic triterpenoid 1 was assigned by spectroscopic data interpretation. To evaluate the activity of compounds 1 and 2, glucose uptake and glucose transporter 4 (GLUT4) translocation were measured in C2C12 myotubes. The C-27-carboxylated triterpenoids 1 and 2 significantly increased basal and insulin-stimulated glucose uptake and GLUT4 translocation to plasma membrane. Both compounds stimulated the phosphorylation of insulin receptor substrate-1 (IRS-1), protein kinase B (Akt), and extracellular signal-regulated kinase 1/2 (Erk1/2). Pretreatment with the Akt inhibitor triciribine or the Erk1/2 inhibitor U0126 decreased the ability of both compounds to enhance basal- and insulin-stimulated glucose uptake and stimulate GLUT4 translocation. These results indicate that compounds 1 and 2 activated both the IRS-1/Akt and Erk1/2 pathways and subsequently stimulated GLUT4 translocation, leading to enhanced glucose uptake. Thus, these observations suggest that C-27-carboxylated-pentacyclic triterpenoids may serve as scaffolds for development as agents for the management of blood glucose levels in disease states such as diabetes.
authors.forename: Joo-Hui
authors.initials: JH
authors.lastname: Han
authors.affiliation: §College of Pharmacy, Yanbian University, Yanji 133002, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: ⊥School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Republic of Korea.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: ∥National Institute of Medicinal Materials, 3B Quang Trung, Hoan Kiem, Hanoi, Vietnam.
authors.forename: Pham Quoc
authors.initials: PQ
authors.lastname: Tuan
authors.affiliation: ∥National Institute of Medicinal Materials, 3B Quang Trung, Hoan Kiem, Hanoi, Vietnam.
authors.forename: Nguyen Minh
authors.initials: NM
authors.lastname: Khoi
authors.affiliation: ∥National Institute of Medicinal Materials, 3B Quang Trung, Hoan Kiem, Hanoi, Vietnam.
authors.forename: Phuong Thien
authors.initials: PT
authors.lastname: Thuong
authors.forename: MinKyun
authors.initials: M
authors.lastname: Na
authors.forename: Chang-Seon
authors.initials: CS
authors.lastname: Myung
mesh_terms: D001692:Biological Transport; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D015394:Molecular Structure; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D053978:Pentacyclic Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D031995:Saxifragaceae / Q000737:chemistry*; D014744:Vietnam
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D053978:Pentacyclic Triterpenes; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose