Upregulation of Glut-4 and PPAR gamma by an isoflavone from Pterocarpus marsupium on L6 myotubes: a possible mechanism of action.
The purpose of the present study is to analyse the influence of Pterocarpus marsupium methanolic extract and isolated Pterocarpus marsupium isoflavone on a battery of cellular targets Glut-4, PPAR gamma and PI3 kinase. Pterocarpus marsupium is an anti-diabetic plant indigenous to South India. Sequential extraction performed with different solvents were analysed for glucose uptake activity at each step. Fraction-9 showing maximum glucose activity on glucose uptake was purified by column chromatography and the structure was elucidated as 7-O-alpha-L-rhamnopyranosyl oxy-4'-methoxy-5-hydroxy isoflavone using NMR and mass spectroscopy. The significant glucose uptake showed by Pterocarpus marsupium crude and pure was comparable with insulin and rosiglitazone. Elevation of Glut-4 and PPARgamma gene expression in parallel with glucose uptake supported the in vitro glucose uptake activity of Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone. The inhibitory effect of cycloheximide on Pterocarpus marsupium methanolic extract and Pterocarpus marsupium isoflavone-mediated glucose uptake suggested that new protein synthesis is required for elevated Glut-4 protein expression. PI3 kinase plays an important role in glucose transport and activated by Pterocarpus marsupium methanolic extract but not the isolated pure isoflavone. Therefore, we postulate that the isoflavone from Pterocarpus marsupium may activate glucose transport by a PI3 kinase independent pathway, which require further analysis.
Anandharajan
R
R
Centre For Biotechnology, Anna University, Chennai 600025, Tamil Nadu, India.
Pathmanathan
K
K
Shankernarayanan
N P
NP
Vishwakarma
Ram A
RA
Balakrishnan
Arun
A
D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D009004:Monosaccharide Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D009124:Muscle Proteins / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D035721:Pterocarpus; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
D051275:Glucose Transporter Type 4; D007529:Isoflavones; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D047495:PPAR gamma; D010936:Plant Extracts; D005947:Glucose