Genistein-derivatives from Tetracera scandens stimulate glucose-uptake in L6 myotubes.
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.
Lee
Myung Sun
MS
Functional Metabolite Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Kim
Chung Hee
CH
Hoang
Duc Manh
DM
Kim
Bo Yeon
BY
Sohn
Cheon Bae
CB
Kim
Mee Ree
MR
Ahn
Jong Seog
JS
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
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