| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,||,1
* Department of Physiology and Pharmacology and
Department of Surgical Sciences at the Karolinska Institutet, Stockholm, Sweden;
Department of Molecular Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden;
Department of Medical Biochemistry and Microbiology and the
|| Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala University, Uppsala Biomedical Center, Uppsala, Sweden
1 Correspondence: Karolinska Institutet, Department of Surgical Sciences, Section of Integrative Physiology, von Eulers väg 4, 4th Floor, S-171 77 Stockholm, Sweden. E-mail: Juleen.Zierath{at}fyfa.ki.se
5'-AMP-activated protein kinase (AMPK) activity is increased during exercise in an intensity- and glycogen-dependent manner. We previously reported that a mutation in the AMPK
3 subunit (Prkag3225Q) increases AMPK activity and skeletal muscle glycogen content. Transfection experiments revealed the R225Q mutation is associated with high basal AMPK activity and diminished AMP dependence. Thus, the R225Q mutation can be considered a loss-of-function mutation that abolished allosteric regulation by AMP/ATP, causing increased basal AMPK activity. We used AMPK3 transgenic (Tg-Prkag3225Q) and knockout (Prkag3–/–) mice to determine the relationship between AMPK activity, glycogen content, and ergogenics (ability to perform work) in isolated extensor digitorum longus skeletal muscle after contractions induced by electrical stimulation. Contraction-induced AMPK activity was inversely coupled to glycogen content in wild-type and Tg-Prkag3225Q mice, but not in Prkag3–/– mice, highlighting a partial feedback control of glycogen on contraction-induced AMPK activity in the presence of a functional AMPK3 isoform. Skeletal muscle glycogen content was positively correlated to work performance, regardless of genotype. Thus, chronic activation of AMPK by the Prkag3225Q mutation directly influences skeletal muscle ergogenics by enhancing glycogen content. In conclusion, functional studies of the AMPK3 isoform further support the close connection between glycogen content and exercise performance in skeletal muscle.—Barnes, B. R., Glund, S., Long, Y. C., Hjälm, G., Andersson, L., Zierath, J. R. 5'-AMP-activated protein kinase regulates skeletal muscle glycogen content and ergogenics.
Key Words: muscle ergogenics • AMPK activity • allosteric regulation • EDL • glycogen supercompensation
This article has been cited by other articles:
|
|
 |
|
  M. E. Osler and J. R. Zierath Minireview: Adenosine 5'-Monophosphate-Activated Protein Kinase Regulation of Fatty Acid Oxidation in Skeletal Muscle Endocrinology, March 1, 2008; 149(3): 935 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Folmes, L. A. Witters, M. F. Allard, M. E. Young, and J. R. B. Dyck The AMPK {gamma}1 R70Q mutant regulates multiple metabolic and growth pathways in neonatal cardiac myocytes Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3456 - H3464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. K. Klein, H. Pilegaard, J. T. Treebak, T. E. Jensen, B. Viollet, P. Schjerling, and J. F. P. Wojtaszewski Lack of AMPK{alpha}2 enhances pyruvate dehydrogenase activity during exercise Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1242 - E1249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Jaswal, M. Gandhi, B. A. Finegan, J. R. B. Dyck, and A. S. Clanachan Inhibition of p38 MAPK and AMPK restores adenosine-induced cardioprotection in hearts stressed by antecedent ischemia by altering glucose utilization Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H1107 - H1114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Barre, C. Richardson, M. F. Hirshman, J. Brozinick, S. Fiering, B. E. Kemp, L. J. Goodyear, and L. A. Witters Genetic model for the chronic activation of skeletal muscle AMP-activated protein kinase leads to glycogen accumulation Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E802 - E811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yu, M. F. Hirshman, N. Fujii, J. M. Pomerleau, L. E. Peter, and L. J. Goodyear Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase {gamma}3-subunit differentially regulates glycogen accumulation Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E557 - E565. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Treebak, S. Glund, A. Deshmukh, D. K. Klein, Y. C. Long, T. E. Jensen, S. B. Jorgensen, B. Viollet, L. Andersson, D. Neumann, et al. AMPK-Mediated AS160 Phosphorylation in Skeletal Muscle Is Dependent on AMPK Catalytic and Regulatory Subunits. Diabetes, July 1, 2006; 55(7): 2051 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Jorgensen, E. A. Richter, and J. F. P. Wojtaszewski Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise J. Physiol., July 1, 2006; 574(1): 17 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Nilsson, Y. C. Long, S. Martinsson, S. Glund, P. Garcia-Roves, L. T. Svensson, L. Andersson, J. R. Zierath, and M. Mahlapuu Opposite Transcriptional Regulation in Skeletal Muscle of AMP-activated Protein Kinase {gamma}3 R225Q Transgenic Versus Knock-out Mice J. Biol. Chem., March 17, 2006; 281(11): 7244 - 7252. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Hardie and K. Sakamoto AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle Physiology, February 1, 2006; 21(1): 48 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. R. Barnes, Y. C. Long, T. L. Steiler, Y. Leng, D. Galuska, J. F.P. Wojtaszewski, L. Andersson, and J. R. Zierath Changes in Exercise-Induced Gene Expression in 5'-AMP-Activated Protein Kinase {gamma}3-Null and {gamma}3 R225Q Transgenic Mice Diabetes, December 1, 2005; 54(12): 3484 - 3489. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
