HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krämer, D. K. Articles by Krook, A. Search for Related Content PubMed PubMed Citation Articles by Krämer, D. K. Articles by Krook, A. Social Bookmarking                What's this?

Direct Activation of Glucose Transport in Primary Human Myotubes After Activation of Peroxisome Proliferator–Activated Receptor

¹ Department of Surgical Science, Karolinska Institute, Stockholm, Sweden
² Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden
³ Gustaf V Research Institute, Karolinska Hospital, Stockholm, Sweden

Activators of peroxisome proliferator–activated receptor (PPAR) have been studied intensively for their insulin-sensitizing properties and antidiabetic effects. Recently, a specific PPAR activator (GW501516) was reported to attenuate plasma glucose and insulin levels when administered to genetically obese ob/ob mice. This study was performed to determine whether specific activation of PPAR has direct effects on insulin action in skeletal muscle. Specific activation of PPAR using two pharmacological agonists (GW501516 and GW0742) increased glucose uptake independently of insulin in differentiated C2C12 myotubes. In cultured primary human skeletal myotubes, GW501516 increased glucose uptake independently of insulin and enhanced subsequent insulin stimulation. PPAR agonists increased the respective phosphorylation and expression of AMP-activated protein kinase 1.9-fold (P < 0.05) and 1.8-fold (P < 0.05), of extracellular signal–regulated kinase 1/2 mitogen-activated protein kinase (MAPK) 2.2-fold (P < 0.05) and 1.7-fold (P < 0.05), and of p38 MAPK 1.2-fold (P < 0.05) and 1.4-fold (P < 0.05). Basal and insulin-stimulated protein kinase B/Akt was unaltered in cells preexposed to PPAR agonists. Preincubation of myotubes with the p38 MAPK inhibitor SB203580 reduced insulin- and PPAR-mediated increase in glucose uptake, whereas the mitogen-activated protein kinase kinase inhibitor PD98059 was without effect. PPAR agonists reduced mRNA expression of PPAR, sterol regulatory element binding protein (SREBP)-1a, and SREBP-1c (P < 0.05). In contrast, mRNA expression of PPAR, PPAR coactivator 1, GLUT1, and GLUT4 was unaltered. Our results provide evidence to suggest that PPAR agonists increase glucose metabolism and promote gene regulatory responses in cultured human skeletal muscle. Moreover, we provide biological validation of PPAR as a potential target for antidiabetic therapy.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E. Nilsson, P. Poulsen, M. Sjogren, C. Ling, M. Ridderstrale, L. Groop, and A. Vaag Regulation of skeletal muscle PPAR{delta} mRNA expression in twins J. Physiol., November 1, 2007; 584(3): 1011 - 1017. [Abstract] [Full Text] [PDF]

				D. K. Kramer, L. Al-Khalili, B. Guigas, Y. Leng, P. M. Garcia-Roves, and A. Krook Role of AMP Kinase and PPAR{delta} in the Regulation of Lipid and Glucose Metabolism in Human Skeletal Muscle J. Biol. Chem., July 6, 2007; 282(27): 19313 - 19320. [Abstract] [Full Text] [PDF]

				Y. Xiong, Q. F. Collins, J. An, E. Lupo Jr., H.-Y. Liu, D. Liu, J. Robidoux, Z. Liu, and W. Cao p38 Mitogen-activated Protein Kinase Plays an Inhibitory Role in Hepatic Lipogenesis J. Biol. Chem., February 16, 2007; 282(7): 4975 - 4982. [Abstract] [Full Text] [PDF]

				D. L. Sprecher, C. Massien, G. Pearce, A. N. Billin, I. Perlstein, T. M. Willson, D. G. Hassall, N. Ancellin, S. D. Patterson, D. C. Lobe, et al. Triglyceride:High-Density Lipoprotein Cholesterol Effects in Healthy Subjects Administered a Peroxisome Proliferator Activated Receptor {delta} Agonist Arterioscler. Thromb. Vasc. Biol., February 1, 2007; 27(2): 359 - 365. [Abstract] [Full Text] [PDF]

				L. Andrulionyte, P. Peltola, J.-L. Chiasson, M. Laakso, and for the STOP-NIDDM Study Group Single Nucleotide Polymorphisms of PPARD in Combination With the Gly482Ser Substitution of PGC-1A and the Pro12Ala Substitution of PPARG2 Predict the Conversion From Impaired Glucose Tolerance to Type 2 Diabetes: The STOP-NIDDM Trial. Diabetes, July 1, 2006; 55(7): 2148 - 2152. [Abstract] [Full Text] [PDF]

				D. J. Baker, P. L. Greenhaff, A. MacInnes, and J. A. Timmons The Experimental Type 2 Diabetes Therapy Glycogen Phosphorylase Inhibition Can Impair Aerobic Muscle Function During Prolonged Contraction Diabetes, June 1, 2006; 55(6): 1855 - 1861. [Abstract] [Full Text] [PDF]

				S. Terada, S. Wicke, J. O. Holloszy, and D.-H. Han PPAR{delta} activator GW-501516 has no acute effect on glucose transport in skeletal muscle Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E607 - E611. [Abstract] [Full Text] [PDF]

				M. Vanttinen, P. Nuutila, T. Kuulasmaa, J. Pihlajamaki, K. Hallsten, K. A. Virtanen, R. Lautamaki, P. Peltoniemi, T. Takala, A. P.M. Viljanen, et al. Single Nucleotide Polymorphisms in the Peroxisome Proliferator-Activated Receptor {delta} Gene Are Associated With Skeletal Muscle Glucose Uptake Diabetes, December 1, 2005; 54(12): 3587 - 3591. [Abstract] [Full Text] [PDF]