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This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/E607    most recent 00430.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Terada, S. Articles by Han, D.-H. Search for Related Content PubMed PubMed Citation Articles by Terada, S. Articles by Han, D.-H.

PPAR activator GW-501516 has no acute effect on glucose transport in skeletal muscle

Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri

Submitted 7 September 2005 ; accepted in final form 1 November 2005

It has been reported that treatment of cultured human skeletal muscle myotubes with the peroxisome proliferator-activated receptor- (PPAR) 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.

peroxisome proliferator-activated receptor-; adenosine monophosphate-activated protein kinase; p38 mitogen-activated protein kinase; insulin; uncoupling protein-3

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