title: Genistein-derivatives from Tetracera scandens stimulate glucose-uptake in L6 myotubes.
abstract: An EtOAc-soluble partition of the MeOH extract of a branch of Tetracera scandens (Dilleniaceae family) was subjected to a glucose-uptake assay, which led to the isolation and identification of five isoflavones of previously known structure namely, genistein (1), its derivatives 3',5'-diprenylgenistein (2), 6,8-diprenylgenistein (3), derrone (4) and alpinumisoflavone (5). Of these, compounds 2--5 exhibited significant glucose-uptake activity in basal and insulin-stimulated L6 myotubes. The findings from adenosine monophosphate-activated kinase (AMPK) activation and glucose transport protein4 (GLUT4) and GLUT1 over-expression revealed certain characteristics of compounds 2--5. These compounds inhibited protein tyrosine phosphatase 1B (PTP1B) activities with IC50 values ranging from 20.63 +/- 0.17 to 37.52 +/- 0.31 microM. No muscle cell toxicity was reported with compounds 3--5, while compounds 1 and 2 reduced muscle cell viability with IC50 values of 34.27 +/- 0.35 and 18.69 +/- 0.19 microM, respectively. It was concluded that T. scandens and its constituents exerted highly desirable activities on type 2 diabetes mellitus treatment since they significantly stimulated the uptake of glucose, AMPK phosphorylation, GLUT4 and GLUT1 mRNA expressions and PTP1B inhibition in L6 myotubes.
authors.affiliation: Functional Metabolite Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Myung Sun
authors.initials: MS
authors.lastname: Lee
authors.forename: Chung Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Duc Manh
authors.initials: DM
authors.lastname: Hoang
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Cheon Bae
authors.initials: CB
authors.lastname: Sohn
authors.forename: Mee Ree
authors.initials: MR
authors.lastname: Kim
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D045466:Dilleniaceae / Q000737:chemistry*; D004789:Enzyme Activation; D019833:Genistein / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D051275:Glucose Transporter Type 4 / Q000096:biosynthesis / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry; D011494:Protein Kinases / Q000378:metabolism; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495694:Slc2a4 protein, rat; D019833:Genistein; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516610:Ptpn1 protein, rat; D005947:Glucose