title: Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle cells in a phosphatidylinositol-3-kinase-independent manner.
abstract: Insulin-stimulated glucose uptake in skeletal muscle is decreased in type 2 diabetes due to impaired translocation of insulin-sensitive glucose transporter 4 (GLUT4) from intracellular pool to plasma membrane. Augmenting glucose uptake into this tissue may help in management of type 2 diabetes. Here, the effects of an identified antihyperglycemic molecule, karanjin, isolated from the fruits of Pongamia pinnata were investigated on glucose uptake and GLUT4 translocation in skeletal muscle cells. Treatment of L6-GLUT4myc myotubes with karanjin caused a substantial increase in the glucose uptake and GLUT4 translocation to the cell surface, in a concentration-dependent fashion, without changing the total amount of GLUT4 protein and GLUT4 mRNA. This effect was associated with increased activity of AMP-activated protein kinase (AMPK). Cycloheximide treatment inhibited the effect of karanjin on GLUT4 translocation suggesting the requirement of de novo synthesis of protein. Karanjin-induced GLUT4 translocation was further enhanced with insulin and the effect is completely protected in the presence of wortmannin. Moreover, karanjin did not affect the phosphorylation of AKT (Ser-473) and did not alter the expression of the key molecules of insulin signaling cascade. We conclude that karanjin-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane associated with activation of AMPK pathway, in a PI-3-K/AKT-independent manner.
authors.affiliation: Division of Biochemistry, Central Drug Research Institute, Council of Scientific and Industrial Research, M.G. Road, Lucknow 226001, India.
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
authors.forename: Akhilesh K
authors.initials: AK
authors.lastname: Tamrakar
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D033641:Millettia / Q000737:chemistry*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D001578:Benzopyrans; D051275:Glucose Transporter Type 4; D007328:Insulin; D012333:RNA, Messenger; D003513:Cycloheximide; D003847:Deoxyglucose; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C052068:karanjin; D000077191:Wortmannin