title: Pongamol from Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells.
abstract: Skeletal muscle is the major site of postprandial glucose disposal and augmenting glucose uptake into this tissue may attenuate insulin resistance that precedes type 2 diabetes mellitus. Here, we investigated the effect of pongamol, an identified lead molecule from the fruits of Pongamia pinnata, on glucose uptake and GLUT4 translocation in skeletal muscle cells. In L6-GLUT4myc myotubes treatment with pongamol significantly promoted both glucose transport and GLUT4 translocation to the cell surface in a concentration-dependent manner, without changing the total amount of GLUT4 protein and GLUT4 mRNA, effects that were also additive with insulin. Cycloheximide treatment inhibited the effect of pongamol on GLUT4 translocation suggesting the requirement of new protein synthesis. The pongamol-induced increase in GLUT4 translocation was completely abolished by wortmannin, and pongamol significantly potentiated insulin-mediated phosphorylation of AKT (Ser-473). We conclude that pongamol-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane, driven by a PI-3-K/AKT dependent mechanism.
authors.affiliation: Division of Biochemistry, Central Drug Research Institute, Council of Scientific and Industrial Research, M.G. Road, Lucknow 226001, India. akhilesh tamrakar@cdri.res.in
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Tamrakar
authors.forename: Natasha
authors.initials: N
authors.lastname: Jaiswal
authors.forename: Prem P
authors.initials: PP
authors.lastname: Yadav
authors.forename: Rakesh
authors.initials: R
authors.lastname: Maurya
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D005638:Fruit / Q000737:chemistry*; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D033641:Millettia / Q000737:chemistry*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D001572:Benzofurans; D051275:Glucose Transporter Type 4; D007328:Insulin; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010936:Plant Extracts; D011994:Recombinant Proteins; C495694:Slc2a4 protein, rat; C533419:pongamol; D003513:Cycloheximide; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D000077191:Wortmannin