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Department of Zoology, Brigham Young University, Provo, Utah 84602; and Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110
Muscle contraction causes an increase in activity of
5'-AMP-activated protein kinase (AMPK). This study was designed
to determine whether chronic chemical activation of AMPK will increase
mitochondrial enzymes, GLUT-4, and hexokinase in different types of
skeletal muscle of resting rats. In acute studies, rats were
subcutaneously injected with either
5-aminoimidazole-4-carboxamide-1-
-D-ribofuranoside (AICAR; 1 mg/g body wt) in 0.9% NaCl or with 0.9% NaCl alone and were
then anesthetized for collection and freezing of tissues. AMPK activity
increased in the superficial, white region of the quadriceps and in
soleus muscles but not in the deep, red region of the quadriceps
muscle. Acetyl-CoA carboxylase (ACC) activity, a target for AMPK,
decreased in all three muscle types in response to AICAR injection but
was lowest in the white quadriceps. In rats given daily, 1 mg/g body
wt, subcutaneous injections of AICAR for 4 wk, activities of citrate
synthase, succinate dehydrogenase, and malate dehydrogenase were
increased in white quadriceps and soleus but not in red quadriceps.
Cytochrome c and 
-aminolevulinic acid synthase levels were
increased in white, but not red, quadriceps. Carnitine
palmitoyl-transferase and hydroxy-acyl-CoA dehydrogenase were not
significantly increased. Hexokinase was markedly increased in all three
muscles, and GLUT-4 was increased in red and white quadriceps. These
results suggest that chronic AMPK activation may mediate the effects of
muscle contraction on some, but not all, biochemical adaptations of
muscle to endurance exercise training.
-aminolevulinate synthase; carnitine palmitoyl transferase; citrate synthase; citric acid cycle enzymes; endurance training; GLUT-4; muscle mitochondria
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E. B. Taylor, D. Hurst, L. J. Greenwood, J. D. Lamb, T. D. Cline, S. N. Sudweeks, and W. W. Winder Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1082 - E1089. [Abstract] [Full Text] [PDF]
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T. Akimoto, T. J. Ribar, R. S. Williams, and Z. Yan Skeletal muscle adaptation in response to voluntary running in Ca2+/calmodulin-dependent protein kinase IV-deficient mice Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1311 - C1319. [Abstract] [Full Text] [PDF]
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 G. R. Steinberg, A. C. Smith, B. J. W. van Denderen, Z. Chen, S. Murthy, D. J. Campbell, G. J. F. Heigenhauser, D. J. Dyck, and B. E. Kemp AMP-Activated Protein Kinase Is Not Down-Regulated in Human Skeletal Muscle of Obese Females J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4575 - 4580. [Abstract] [Full Text] [PDF]
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J. A. Villena, B. Viollet, F. Andreelli, A. Kahn, S. Vaulont, and H. S. Sul Induced Adiposity and Adipocyte Hypertrophy in Mice Lacking the AMP-Activated Protein Kinase-{alpha}2 Subunit Diabetes, September 1, 2004; 53(9): 2242 - 2249. [Abstract] [Full Text] [PDF]
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D. Nagata, R. Takeda, M. Sata, H. Satonaka, E. Suzuki, T. Nagano, and Y. Hirata AMP-Activated Protein Kinase Inhibits Angiotensin II-Stimulated Vascular Smooth Muscle Cell Proliferation Circulation, July 27, 2004; 110(4): 444 - 451. [Abstract] [Full Text] [PDF]
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E.-K. Kim, I. Miller, S. Aja, L. E. Landree, M. Pinn, J. McFadden, F. P. Kuhajda, T. H. Moran, and G. V. Ronnett C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase J. Biol. Chem., May 7, 2004; 279(19): 19970 - 19976. [Abstract] [Full Text] [PDF]
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S. A. Clark, Z.-P. Chen, K. T. Murphy, R. J. Aughey, M. J. McKenna, B. E. Kemp, and J. A. Hawley Intensified exercise training does not alter AMPK signaling in human skeletal muscle Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E737 - E743. [Abstract] [Full Text] [PDF]
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U. Andersson, K. Filipsson, C. R. Abbott, A. Woods, K. Smith, S. R. Bloom, D. Carling, and C. J. Small AMP-activated Protein Kinase Plays a Role in the Control of Food Intake J. Biol. Chem., March 26, 2004; 279(13): 12005 - 12008. [Abstract] [Full Text] [PDF]
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C. Frosig, S. B. Jorgensen, D. G. Hardie, E. A. Richter, and J. F. P. Wojtaszewski 5'-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle Am J Physiol Endocrinol Metab, March 1, 2004; 286(3): E411 - E417. [Abstract] [Full Text]
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S. Terada and I. Tabata Effects of acute bouts of running and swimming exercise on PGC-1{alpha} protein expression in rat epitrochlearis and soleus muscle Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E208 - E216. [Abstract] [Full Text] [PDF]
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S. B. Jorgensen, B. Viollet, F. Andreelli, C. Frosig, J. B. Birk, P. Schjerling, S. Vaulont, E. A. Richter, and J. F. P. Wojtaszewski Knockout of the {alpha}2 but Not {alpha}1 5'-AMP-activated Protein Kinase Isoform Abolishes 5-Aminoimidazole-4-carboxamide-1-{beta}-4-ribofuranosidebut Not Contraction-induced Glucose Uptake in Skeletal Muscle J. Biol. Chem., January 9, 2004; 279(2): 1070 - 1079. [Abstract] [Full Text] [PDF]
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J. Norrbom, C. J. Sundberg, H. Ameln, W. E. Kraus, E. Jansson, and T. Gustafsson PGC-1{alpha} mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle J Appl Physiol, January 1, 2004; 96(1): 189 - 194. [Abstract] [Full Text] [PDF]
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N. B. Ruderman, A. K. Saha, and E. W. Kraegen Minireview: Malonyl CoA, AMP-Activated Protein Kinase, and Adiposity Endocrinology, December 1, 2003; 144(12): 5166 - 5171. [Abstract] [Full Text] [PDF]
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M. Suwa, H. Nakano, and S. Kumagai Effects of chronic AICAR treatment on fiber composition, enzyme activity, UCP3, and PGC-1 in rat muscles J Appl Physiol, September 1, 2003; 95(3): 960 - 968. [Abstract] [Full Text] [PDF]
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K. BAAR, Z. SONG, C. F. SEMENKOVICH, T. E. JONES, D.-H. HAN, L. A. NOLTE, E. O. OJUKA, M. CHEN, and J. O. HOLLOSZY Skeletal muscle overexpression of nuclear respiratory factor 1 increases glucose transport capacity FASEB J, September 1, 2003; 17(12): 1666 - 1673. [Abstract] [Full Text] [PDF]
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C. T Putman, M. Kiricsi, J. Pearcey, I. M MacLean, J. A Bamford, G. K Murdoch, W. T Dixon, and D. Pette AMPK activation increases uncoupling protein-3 expression and mitochondrial enzyme activities in rat muscle without fibre type transitions J. Physiol., August 15, 2003; 551(1): 169 - 178. [Abstract] [Full Text] [PDF]
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S. I. Itani, A. K. Saha, T. G. Kurowski, H. R. Coffin, K. Tornheim, and N. B. Ruderman Glucose Autoregulates Its Uptake in Skeletal Muscle: Involvement of AMP-Activated Protein Kinase Diabetes, July 1, 2003; 52(7): 1635 - 1640. [Abstract] [Full Text] [PDF]
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E. O. OJUKA, T. E. JONES, D.-H. HAN, M. CHEN, and J. O. HOLLOSZY Raising Ca2+ in L6 myotubes mimics effects of exercise on mitochondrial biogenesis in muscle FASEB J, April 1, 2003; 17(6): 675 - 681. [Abstract] [Full Text] [PDF]
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N. Jessen, R. Pold, E. S. Buhl, L. S. Jensen, O. Schmitz, and S. Lund Effects of AICAR and exercise on insulin-stimulated glucose uptake, signaling, and GLUT-4 content in rat muscles J Appl Physiol, April 1, 2003; 94(4): 1373 - 1379. [Abstract] [Full Text] [PDF]
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S. L. McGee, K. F. Howlett, R. L. Starkie, D. Cameron-Smith, B. E. Kemp, and M. Hargreaves Exercise Increases Nuclear AMPK {alpha}2 in Human Skeletal Muscle Diabetes, April 1, 2003; 52(4): 926 - 928. [Abstract] [Full Text] [PDF]
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K. Hojlund, K. Wrzesinski, P. M. Larsen, S. J. Fey, P. Roepstorff, A. Handberg, F. Dela, J. Vinten, J. G. McCormack, C. Reynet, et al. Proteome Analysis Reveals Phosphorylation of ATP Synthase beta -Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes J. Biol. Chem., March 14, 2003; 278(12): 10436 - 10442. [Abstract] [Full Text] [PDF]
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J. N. Nielsen, K. J. W. Mustard, D. A. Graham, H. Yu, C. S. MacDonald, H. Pilegaard, L. J. Goodyear, D. G. Hardie, E. A. Richter, and J. F. P. Wojtaszewski 5'-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle J Appl Physiol, February 1, 2003; 94(2): 631 - 641. [Abstract] [Full Text] [PDF]
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M. Yu, N. K Stepto, A. V Chibalin, L. G D Fryer, D. Carling, A. Krook, J. A Hawley, and J. R Zierath Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise J. Physiol., January 15, 2003; 546(2): 327 - 335. [Abstract] [Full Text] [PDF]
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T. Daniel and D. Carling Functional Analysis of Mutations in the gamma 2 Subunit of AMP-activated Protein Kinase Associated with Cardiac Hypertrophy and Wolff-Parkinson-White Syndrome J. Biol. Chem., December 20, 2002; 277(52): 51017 - 51024. [Abstract] [Full Text] [PDF]
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H. Zong, J. M. Ren, L. H. Young, M. Pypaert, J. Mu, M. J. Birnbaum, and G. I. Shulman AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation PNAS, December 10, 2002; 99(25): 15983 - 15987. [Abstract] [Full Text] [PDF]
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E. Tomas, T.-S. Tsao, A. K. Saha, H. E. Murrey, C. c. Zhang, S. I. Itani, H. F. Lodish, and N. B. Ruderman Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation PNAS, December 10, 2002; 99(25): 16309 - 16313. [Abstract] [Full Text] [PDF]
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J. Stoppani, A. L. Hildebrandt, K. Sakamoto, D. Cameron-Smith, L. J. Goodyear, and P. D. Neufer AMP-activated protein kinase activates transcription of the UCP3 and HKII genes in rat skeletal muscle Am J Physiol Endocrinol Metab, December 1, 2002; 283(6): E1239 - E1248. [Abstract] [Full Text] [PDF]
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E. O. Ojuka, T. E. Jones, D.-H. Han, M. Chen, B. R. Wamhoff, M. Sturek, and J. O. Holloszy Intermittent increases in cytosolic Ca2+ stimulate mitochondrial biogenesis in muscle cells Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E1040 - E1045. [Abstract] [Full Text] [PDF]
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M. A. Iglesias, J.-M. Ye, G. Frangioudakis, A. K. Saha, E. Tomas, N. B. Ruderman, G. J. Cooney, and E. W. Kraegen AICAR Administration Causes an Apparent Enhancement of Muscle and Liver Insulin Action in Insulin-Resistant High-Fat-Fed Rats Diabetes, October 1, 2002; 51(10): 2886 - 2894. [Abstract] [Full Text] [PDF]
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B. R. Barnes, J. W. Ryder, T. L. Steiler, L. G.D. Fryer, D. Carling, and J. R. Zierath Isoform-Specific Regulation of 5' AMP-Activated Protein Kinase in Skeletal Muscle From Obese Zucker (fa/fa) Rats in Response to Contraction Diabetes, September 1, 2002; 51(9): 2703 - 2708. [Abstract] [Full Text] [PDF]
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H. Park, V. K. Kaushik, S. Constant, M. Prentki, E. Przybytkowski, N. B. Ruderman, and A. K. Saha Coordinate Regulation of Malonyl-CoA Decarboxylase, sn-Glycerol-3-phosphate Acyltransferase, and Acetyl-CoA Carboxylase by AMP-activated Protein Kinase in Rat Tissues in Response to Exercise J. Biol. Chem., August 30, 2002; 277(36): 32571 - 32577. [Abstract] [Full Text] [PDF]
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