title: PPARdelta activator GW-501516 has no acute effect on glucose transport in skeletal muscle.
abstract: It has been reported that treatment of cultured human skeletal muscle myotubes with the peroxisome proliferator-activated receptor-delta (PPARdelta) activator GW-501516 directly stimulates glucose transport and enhances insulin action. Cultured myotubes are minimally responsive to insulin stimulation of glucose transport and are not a good model for studying skeletal muscle glucose transport. The purpose of this study was to evaluate the effect of GW-501516 on glucose transport to determine whether the findings on cultured myotubes have relevance to skeletal muscle. Rat epitrochlearis and soleus muscles were treated for 6 h with 10, 100, or 500 nM GW-501516, followed by measurement of 2-deoxyglucose uptake. GW-501516 had no effect on glucose uptake. There was no effect on insulin sensitivity or responsiveness. Also, in contrast to findings on myotubes, treatment of muscles with GW-501516 did not result in increased phosphorylation or increased expression of AMP-activated protein kinase (AMPK) or p38 mitogen-activated protein kinase (MAPK). Treatment of epitrochlearis muscles with GW-501516 for 24 h induced a threefold increase in uncoupling protein-3 mRNA, providing evidence that the GW-501516 compound that we used gets into and is active in skeletal muscle. In conclusion, our results show that, in contrast to myotubes in culture, skeletal muscle does not respond to GW-501516 with 1) an increase in AMPK or p38 MAPK phosphorylation or expression or 2) direct stimulation of glucose transport or enhanced insulin action.
authors.affiliation: Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Shin
authors.initials: S
authors.lastname: Terada
authors.forename: Scott
authors.initials: S
authors.lastname: Wicke
authors.forename: John O
authors.initials: JO
authors.lastname: Holloszy
authors.forename: Dong-Ho
authors.initials: DH
authors.lastname: Han
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels; D008297:Male; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology*; D000071247:Uncoupling Protein 3; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C425931:GW 501516; D051275:Glucose Transporter Type 4; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D047494:PPAR delta; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D013844:Thiazoles; C000604392:UCP3 protein, human; C000604393:Ucp3 protein, mouse; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose