Contraction-induced Changes in Acetyl-CoA Carboxylase and 5′-AMP-activated Kinase in Skeletal Muscle
Open accessAbstract
The concentration of malonyl-CoA, a negative regulator of fatty acid oxidation, diminishes acutely in contracting skeletal muscle. To determine how this occurs, the activity and properties of acetyl-CoA carboxylase beta (ACC-beta), the skeletal muscle isozyme that catalyzes malonyl-CoA formation, were examined in rat gastrocnemius-soleus muscles at rest and during contractions induced by electrical stimulation of the sciatic nerve. To avoid the problem of contamination of the muscle extract by mitochondrial carboxylases, an assay was developed in which ACC-beta was first purified by immunoprecipitation with a monoclonal antibody. ACC-beta was quantitatively recovered in the immunopellet and exhibited a high sensitivity to citrate (12-fold activation) and a Km for acetyl-CoA (120 microM) similar to that reported for ACC-beta purified by other means. After 5 min of contraction, ACC-beta activity was decreased by 90% despite an apparent increase in the cytosolic concentration of citrate, a positive regulator of ACC. SDS-polyacrylamide gel electrophoresis of both homogenates and immunopellets from these muscles showed a decrease in the electrophoretic mobility of ACC, suggesting that phosphorylation could account for the decrease in ACC activity. In keeping with this notion, citrate activation of ACC purified from contracting muscle was markedly depressed. In addition, homogenization of the muscles in a buffer free of phosphatase inhibitors and containing the phosphatase activators glutamate and MgCl2 or treatment of immunoprecipitated ACC-beta with purified protein phosphatase 2A abolished the decreases in both ACC-beta activity and electrophoretic mobility caused by contraction. The rapid decrease in ACC-beta activity after the onset of contractions (50% by 20 s) and its slow restoration to initial values during recovery (60-90 min) were paralleled temporally by reciprocal changes in the activity of the alpha2 but not the alpha1 isoform of 5'-AMP-activated protein kinase (AMPK). In conclusion, the results suggest that the decrease in ACC activity during muscle contraction is caused by an increase in its phosphorylation, most probably due, at least in part, to activation of the alpha2 isoform of AMPK. They also suggest a dual mechanism for ACC regulation in muscle in which inhibition by phosphorylation takes precedence over activation by citrate. These alterations in ACC and AMPK activity, by diminishing the concentration of malonyl-CoA, could be responsible for the increase in fatty acid oxidation observed in skeletal muscle during exercise.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
AMPK is activated during exercise in both rodents and humans.
“Consistent with this, AMPK is activated during exercise in both rodents and humans [51-60], in an intensity-dependent manner [57,59-61].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [56]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Mammalian AMP-activated protein kinase subfamily
Stapleton, D., Mitchelhill, K. I., Gao, G., Widmer, J., Michell, B. J., Teh, T., House, C. M., Fernandez, C. S., Cox, T., Witters, L. A., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.611 · Cited by 652 · see citing works
Self-citation(1995) · FEBS Letters · doi:10.1016/0014-5793(95)01368-7 · Cited by 595 · see citing works
Kudo, N., Barr, A., Barr, R. L., Desai, S. S., & Lopaschuk, G. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17513 · Cited by 565 · see citing works
McGarry, J. D., Mills, S. E., Long, C. S., & Foster, D. W. (1983) · Biochemical Journal · doi:10.1042/bj2140021 · Cited by 556 · see citing works
Hawley, S. A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., & Hardie, D. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.45.27186 · Cited by 441 · see citing works
Role of the AMP-activated protein kinase in the cellular stress response
Corton, J. M., Gillespie, J. G., & Hardie, D. G. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00070-1 · Cited by 423 · see citing works
Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart.
Saddik, M., Gamble, J., Witters, L. A., & Lopaschuk, G. D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74465-2 · Cited by 390 · see citing works
Self-citationRegulation of ketogenesis and the renaissance of carnitine palmitoyltransferase
McGarry, J., Woeltje, K. F., Kuwajima, M., & Foster, D. W. (1989) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610050305 · Cited by 354 · see citing works
Critical phosphorylation sites for acetyl-CoA carboxylase activity.
Ha, J., Daniel, S., Broyles, S. S., & Kim, K. H. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31770-2 · Cited by 328 · see citing works
Identification of an isozymic form of acetyl-CoA carboxylase.
Bianchi, A., Evans, J. L., Iverson, A. J., Nordlund, A. C., Watts, T. D., & Witters, L. A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)40045-8 · Cited by 261 · see citing works
Self-citationSidossis, L. S., Stuart, C. A., Shulman, G. I., Lopaschuk, G. D., & Wolfe, R. R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci119034 · Cited by 233 · see citing works
Witters, L. A., & Kemp, B. E. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50663-9 · Cited by 228 · see citing works
Self-citationRole of reversible phosphorylation of acetyl‐CoA carboxylase in long‐chain fatty acid synthesis 1
Kim, K., López‐Casillas, F., Bai, D.-H., Luo, X., & Pape, M. E. (1989) · The FASEB Journal · doi:10.1096/fasebj.3.11.2570725 · Cited by 201 · see citing works
Malonyl-CoA metabolism in cardiac myocytes and its relevance to the control of fatty acid oxidation
Awan, M. M., & SAGGERSON, E. D. (1993) · Biochemical Journal · doi:10.1042/bj2950061 · Cited by 196 · see citing works
Regulation of fatty acid synthesis via phosphorylation of acetyl-CoA carboxylase
Hardie, D. G. (1989) · Progress in Lipid Research · doi:10.1016/0163-7827(89)90010-6 · Cited by 191 · see citing works
McGarry, J., Stark, M. J., & Foster, D. W. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34394-6 · Cited by 188 · see citing works
Regulation of 5′-AMP-activated Protein Kinase Activity by the Noncatalytic β and γ Subunits
Dyck, J. R. B., Gao, G., Widmer, J., Stapleton, D., Fernández, C., Kemp, B. E., & Witters, L. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.30.17798 · Cited by 185 · see citing works
Self-citationRegulation of fatty acid and cholesterol metabolism by the AMP-activated protein kinase
Hardie, D. G. (1992) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(92)90001-c · Cited by 181 · see citing works
DAVIES, S. P., Carling, D., Munday, M. R., & Hardie, D. G. (1992) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1992.tb16591.x · Cited by 179 · see citing works
The AMP-activated protein kinase: a multisubstrate regulator of lipid metabolism
Hardie, D. G., Carling, D., & Sim, A. T. R. (1989) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(89)90084-4 · Cited by 178 · see citing works
Formation of malonyl coenzyme A in rat heart
Thampy, K. G. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84614-8 · Cited by 153 · see citing works
Katsurada, A., Iritani, N., Fukuda, H., Matsumura, Y., NISHIMOTO, N., Noguchi, T., & Tanaka, T. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15593.x · Cited by 147 · see citing works
Cloning of human acetyl-CoA carboxylase-beta and its unique features.
Ha, J., Lee, J., Kim, K. S., Witters, L. A., & Kim, K. H. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.21.11466 · Cited by 146 · see citing works
Self-citationInfluence of acidosis on AMP deaminase activity in contracting fast-twitch muscle
Dudley, G. A., & Terjung, R. L. (1985) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1985.248.1.c43 · Cited by 139 · see citing works
Sugden, P. H., & Newsholme, E. A. (1975) · Biochemical Journal · doi:10.1042/bj1500113 · Cited by 130 · see citing works
Non-catalytic - and -Subunit Isoforms of the 5′-AMP-activated Protein Kinase
Gao, G., Fernández, C., Stapleton, D., Auster, A. S., Widmer, J., Dyck, J. R. B., Kemp, B. E., & Witters, L. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8675 · Cited by 129 · see citing works
Self-citationStapleton, D., Gao, G., Michell, B. J., Widmer, J., Mitchelhill, K. I., Teh, T., House, C. M., Witters, L. A., & Kemp, B. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43879-3 · Cited by 122 · see citing works
Self-citationDavies, J., & Riechmann, L. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)01313-x · Cited by 122 · see citing works
Cook, G. A. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)71315-3 · Cited by 115 · see citing works
Insulin stimulates the dephosphorylation and activation of acetyl-CoA carboxylase.
Witters, L. A., Watts, T. D., Daniels, D., & Evans, J. L. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.15.5473 · Cited by 114 · see citing works
Self-citationMcGarry, J. (1995) · Biochemical Society Transactions · doi:10.1042/bst0230321 · Cited by 106 · see citing works
Assimacopoulos‐Jeannet, F., Brichard, S. M., Rencurel, F., Cusin, I., & Jeanrenaud, B. (1995) · Metabolism · doi:10.1016/0026-0495(95)90270-8 · Cited by 95 · see citing works
Regulation of Acetyl-CoA Carboxylase
Kim, K.-H. (1983) · Current topics in cellular regulation · doi:10.1016/b978-0-12-152822-5.50009-9 · Cited by 84 · see citing works
Immunological analysis of acetyl-CoA carboxylase mass, tissue distribution and subunit composition
Iverson, A. J., Bianchi, A., Nordlund, A. C., & Witters, L. A. (1990) · Biochemical Journal · doi:10.1042/bj2690365 · Cited by 84 · see citing works
Self-citationGao, G., Widmer, J., Stapleton, D., Teh, T., Cox, T. M., Kemp, B. E., & Witters, L. A. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(94)00222-z · Cited by 82 · see citing works
Self-citationWinz, R. A., Hess, D., Aebersold, R. H., & Brownsey, R. W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36642-5 · Cited by 81 · see citing works
Sarcomere dynamics during isotonic velocity transients in single frog muscle fibers
Granzier, H. L. M., MATTIAZZI, A. R., & Pollack, G. H. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.259.2.c266 · Cited by 79 · see citing works
Beaty, N. B., & Lane, M. D. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44077-4 · Cited by 77 · see citing works
Thampy, K. G., & Wakil, S. J. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68807-6 · Cited by 77 · see citing works
Identification of a second human acetyl-CoA carboxylase gene
Widmer, J., FASSIHI, K. S., SCHLICHTER, S. C., WHEELER, K. S., Crute, B. E., Nicole, K. I. N. G., Nutile‐McMenemy, N., Noll, W. W., Daniel, S., Ha, J., et al. (1996) · Biochemical Journal · doi:10.1042/bj3160915 · Cited by 75 · see citing works
Self-citationThampy, K. G., & Wakil, S. J. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)68808-8 · Cited by 70 · see citing works
Gillespie, J. G., & Hardie, D. G. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)80837-7 · Cited by 69 · see citing works
The polymerization of acetyl-CoA carboxylase.
Beaty, N. B., & Lane, M. D. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44078-6 · Cited by 63 · see citing works
Beaty, N. B., & Lane, M. D. (1982) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68288-8 · Cited by 54 · see citing works
Effect of fasting and refeeding on acetyl-CoA carboxylase in rat hindlimb muscle
Winder, W. W., MacLean, P. S., Lucas, J. C., Fernley, J. E., & Trumble, G. E. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.2.578 · Cited by 51 · see citing works
Regulation of mitochondrial carnitine palmitoyl transferases from liver and extrahepatic tissues
Saggerson, D., Ghadiminejad, I., & Awan, M. (1992) · Advances in Enzyme Regulation · doi:10.1016/0065-2571(92)90023-s · Cited by 51 · see citing works
Pattern and Regulation of Acetyl-CoA Carboxylase Gene Expression
Kim, K.-H., & Tae, H.-J. (1994) · Journal of Nutrition · doi:10.1093/jn/124.suppl_8.1273s · Cited by 48 · see citing works
AMP‐activated protein kinase ‐ An archetypal protein kinase cascade?
Hardie, D. G., & MacKintosh, R. W. (1992) · BioEssays · doi:10.1002/bies.950141011 · Cited by 47 · see citing works
Gaussin, V., Hue, L., Stalmans, W., & Bollen, M. (1996) · Biochemical Journal · doi:10.1042/bj3160217 · Cited by 46 · see citing works
Glucose regulation of acetyl-CoA carboxylase in hepatoma and islet cells.
Louis, N. A., & Witters, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45876-0 · Cited by 44 · see citing works
Self-citationZierz, S., & Engel, A. G. (1987) · Biochemical Journal · doi:10.1042/bj2450205 · Cited by 43 · see citing works
Effect of glucose infusion on muscle malonyl-CoA during exercise
Elayan, I., & Winder, W. W. (1991) · Journal of Applied Physiology · doi:10.1152/jappl.1991.70.4.1495 · Cited by 42 · see citing works
Effect of epinephrine on acetyl-CoA carboxylase in rat epididymal fat tissue.
Lee, K. H., & Kim, K. H. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34375-2 · Cited by 33 · see citing works
Nerve stimulation decreases malonyl-CoA in skeletal muscle
Duan, C., & Winder, W. W. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.72.3.901 · Cited by 33 · see citing works
Evidence of a biotin dependent acetyl-coenzyme a carboxylase in rat muscle
Trumble, G. E., Smith, M. A., & Winder, W. W. (1991) · Life Sciences · doi:10.1016/0024-3205(91)90577-x · Cited by 22 · see citing works
Bianchi, A., Evans, J. L., Nordlund, A. C., Watts, T. D., & Witters, L. A. (1992) · Journal of Cellular Biochemistry · doi:10.1002/jcb.240480113 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 5
- Ha, J., Lee, J. K., Kim, K. S., Witters, L. A., and Kim, K. H. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 11466 -11470
- Witters, L. A., Watts, T. D., Daniels, D. L., and Evans, J. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 5473-5477
- Hardie, D. G. (1989) Proc. Lipid Res. 28, 117-146
- McGarry, J. D. (1995) Biochem. Soc. Trans. 23, 321-324
- Barman, T. (1969) in Enzyme Handbook, Vol. 2, pp. 912-914, Springer-Verlag New York Inc., New York
Cited by
Sorted by citations
Fiber Types in Mammalian Skeletal Muscles
Schiaffino, S., & Reggiani, C. (2011) · Physiological Reviews · doi:10.1152/physrev.00031.2010 · Cited by 3,022 · see citing works
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491 · see citing works
Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
Minokoshi, Y., Kim, Y.-B., Peroni, O. D., Fryer, L. G. D., Müller, C., Carling, D., & Kahn, B. B. (2002) · Nature · doi:10.1038/415339a · Cited by 2,053 · see citing works
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,633 · see citing works
Self-citationTHE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,436 · see citing works
Xu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151 · see citing works
The AMP-activated protein kinase pathway – new players upstream and downstream
Hardie, D. G. (2004) · Journal of Cell Science · doi:10.1242/jcs.01540 · Cited by 1,136 · see citing works
Merrill, G. F., Kurth, E. J., Hardie, D. G., & Winder, W. W. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.6.e1107 · Cited by 1,027 · see citing works
AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes
Winder, W. W., & Hardie, D. G. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.1.e1 · Cited by 1,000 · see citing works
Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status
Hardie, D. G. (2003) · Endocrinology · doi:10.1210/en.2003-0982 · Cited by 994 · see citing works
Tomas, E., Tsao, T.-S., Saha, A. K., Murrey, H. E., Zhang, C. C., Itani, S. I., Lodish, H. F., & Ruderman, N. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.222657499 · Cited by 973 · see citing works
Self-citationMu, J., Brozinick, J. T., Valladares, O., Bucan, M., & Birnbaum, M. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00251-9 · Cited by 924 · see citing works
Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2
Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. H., & Wakil, S. J. (2001) · Science · doi:10.1126/science.1056843 · Cited by 903 · see citing works
AMPK, insulin resistance, and the metabolic syndrome
Ruderman, N. B., Carling, D., Prentki, M., & Cacicedo, J. M. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67227 · Cited by 877 · see citing works
Self-citationBolster, D. R., Crozier, S. J., Kimball, S. R., & Jefferson, L. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200171200 · Cited by 851 · see citing works
The randle cycle revisited: a new head for an old hat.
Hue, L., & Taegtmeyer, H. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2009 · Cited by 743 · see citing works
Malonyl-CoA, fuel sensing, and insulin resistance
Ruderman, N. B., Saha, A. K., Vavvas, D. G., & Witters, L. A. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.1.e1 · Cited by 644 · see citing works
Self-citationNawrocki, A. R., Rajala, M. W., Tomás, E., Pajvani, U. B., Saha, A. K., Trumbauer, M. E., Pang, Z., Chen, A. S., Ruderman, N. B., Chen, H., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505311200 · Cited by 640 · see citing works
Self-citationCharacterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding
CHEUNG, P. C. F., SALT, I. P., DAVIES, S. P., HARDIE, D. G., & CARLING, D. (2000) · Biochemical Journal · doi:10.1042/bj3460659 · Cited by 637 · see citing works
Jørgensen, S. B., Viollet, B., Andreelli, F., Frøsig, C., Birk, J. B., Schjerling, P., Vaulont, S., Richter, E. A., & Wojtaszewski, J. F. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306205200 · Cited by 553 · see citing works
Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR
Russell, R. R., Bergeron, R., Shulman, G. I., & Young, L. H. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.2.h643 · Cited by 553 · see citing works
Laker, R. C., Drake, J. C., Wilson, R. J., Lira, V. A., Lewellen, B. M., Ryall, K. A., Fisher, C. C., Zhang, M., Saucerman, J. J., Goodyear, L. J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00520-9 · Cited by 529 · see citing works
Dealing with energy demand: the AMP-activated protein kinase
Kemp, B. E., Mitchelhill, K. I., Stapleton, D., Michell, B. J., Chen, Z., & Witters, L. A. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01340-1 · Cited by 521 · see citing works
Self-citationAMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle
Hardie, D. G., & Sakamoto, K. (2006) · Physiology · doi:10.1152/physiol.00044.2005 · Cited by 519 · see citing works
The AMP-activated protein kinase α2 catalytic subunit controls whole-body insulin sensitivity
Viollet, B., Andreelli, F., Jørgensen, S. B., Perrin, C., Geloen, A., Flamez, D., Mu, J., Lenzner, C., Baud, O., Bennoun, M., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci16567 · Cited by 499 · see citing works
Skeletal Muscle Lipid Metabolism in Exercise and Insulin Resistance
Kiens, B. (2006) · Physiological Reviews · doi:10.1152/physrev.00023.2004 · Cited by 478 · see citing works
AMP kinase and malonyl-CoA: targets for therapy of the metabolic syndrome
Ruderman, N., & Prentki, M. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1344 · Cited by 451 · see citing works
Self-citationSalt, I. P., Celler, J. W., Hawley, S. A., Prescott, A. R., Woods, A., Carling, D., & Hardie, D. G. (1998) · Biochemical Journal · doi:10.1042/bj3340177 · Cited by 437 · see citing works
Wojtaszewski, J. F. P., Nielsen, P., Hansen, B. F., Richter, E. A., & Kiens, B. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00221.x · Cited by 435 · see citing works
AMPK activation: a therapeutic target for type 2 diabetes?
Saha, A. K., Coughlan, K. A., Valentine, R. J., & Ruderman, N. B. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s43731 · Cited by 440 · see citing works
Self-citationAMP-activated protein kinase and its downstream transcriptional pathways
Cantó, C., & Auwerx, J. (2010) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-010-0454-z · Cited by 421 · see citing works
Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy.
Booth, F., Chakravarthy, M., Gordon, S., & Spangenburg, E. (2002) · Journal of applied physiology · doi:10.1152/japplphysiol.00073.2002 · Cited by 467 · see citing works
AMP-Activated Protein Kinase as a Drug Target
Hardie, D. G. (2006) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105304 · Cited by 405 · see citing works
Salt, I. P., JOHNSON, G., Ashcroft, S. J. H., & Hardie, D. G. (1998) · Biochemical Journal · doi:10.1042/bj3350533 · Cited by 408 · see citing works
Woods, A., Azzout‐Marniche, D., Foretz, M., STEIN, S. C., Lemarchand, P., Ferré, P., Foufelle, F., & Carling, D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6704-6711.2000 · Cited by 404 · see citing works
AMPK alterations in cardiac physiology and pathology: enemy or ally?
Dyck, J. R. B., & Lopaschuk, G. D. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109389 · Cited by 386 · see citing works
Park, H., Kaushik, V. K., Constant, S., Prentki, M., Przybytkowski, E., Ruderman, N. B., & Saha, A. K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201692200 · Cited by 384 · see citing works
Self-citationEnergy-sensing and signaling by AMP-activated protein kinase in skeletal muscle
Winder, W. W. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1017 · Cited by 375 · see citing works
Musi, N., Fujii, N., Hirshman, M. F., Ekberg, I., Fröberg, S., Ljungqvist, O., Thorell, A., & Goodyear, L. J. (2001) · Diabetes · doi:10.2337/diabetes.50.5.921 · Cited by 371 · see citing works
Skeletal Muscle Glucose Uptake During Exercise: How is it Regulated?
Rose, A. J., & Richter, E. A. (2005) · Physiology · doi:10.1152/physiol.00012.2005 · Cited by 371 · see citing works
Effect of Exercise Intensity on Skeletal Muscle AMPK Signaling in Humans
Chen, Z.-P., Stephens, T. J., Murthy, S., Canny, B. J., Hargreaves, M., Witters, L. A., Kemp, B. E., & McConell, G. K. (2003) · Diabetes · doi:10.2337/diabetes.52.9.2205 · Cited by 369 · see citing works
Self-citationInsulin action and insulin resistance in human skeletal muscle
Zierath, J. R., Krook, A., & Wallberg-Henriksson, H. (2000) · Diabetologia · doi:10.1007/s001250051457 · Cited by 367 · see citing works
The Development of Porcine Models of Obesity and the Metabolic Syndrome ,
Spurlock, M. E., & Gabler, N. K. (2008) · Journal of Nutrition · doi:10.1093/jn/138.2.397 · Cited by 365 · see citing works
AMP-Activated Protein Kinase: An Ultrasensitive System for Monitoring Cellular Energy Charge
HARDIE, D. G., SALT, I. P., HAWLEY, S. A., & DAVIES, S. P. (1999) · Biochemical Journal · doi:10.1042/bj3380717 · Cited by 362 · see citing works
Fujii, N., Hayashi, T., Hirshman, M. F., Smith, J. T., Habinowski, S. A., Kaijser, L., Mu, J., Ljungqvist, O., Birnbaum, M. J., Witters, L. A., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3073 · Cited by 351 · see citing works
Self-citationWojtaszewski, J. F. P., MacDonald, C., Nielsen, J. N., Hellsten, Y., Hardie, D. G., Kemp, B. E., Kiens, B., & Richter, E. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00436.2002 · Cited by 348 · see citing works
Self-citationExercise as a therapeutic intervention for the prevention and treatment of insulin resistance
Hawley, J. A. (2004) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.505 · Cited by 344 · see citing works
Chen, Z., McConell, G. K., Michell, B. J., Snow, R. J., Canny, B. J., & Kemp, B. E. (2000) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2000.279.5.e1202 · Cited by 342 · see citing works
Self-citationCulmsee, C., monnig, J., Kemp, B. E., & Mattson, M. P. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:1:45 · Cited by 340 · see citing works
Self-citationSanchez, A. M. J., Csibi, A., Raibon, A., Cornille, K., Gay, S., Bernardi, H., & Candau, R. B. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23399 · Cited by 329 · see citing works
Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis
Rutter, G. A., Xavier, G. D. S., & Leclerc, I. (2003) · Biochemical Journal · doi:10.1042/bj20030048 · Cited by 328 · see citing works
Chemistry and Biochemistry of Type 2 Diabetes
Ross, S. A., Gulve, E. A., & Wang, M. (2004) · Chemical Reviews · doi:10.1021/cr0204653 · Cited by 326 · see citing works
Ponticos, M., Lu, Q. L., Morgan, J. E., Hardie, D. G., Partridge, T. A., & Carling, D. (1998) · The EMBO Journal · doi:10.1093/emboj/17.6.1688 · Cited by 317 · see citing works
Kramer, H. F., Witczak, C. A., Fujii, N., Jessen, N., Taylor, E. B., Arnolds, D. E., Sakamoto, K., Hirshman, M. F., & Goodyear, L. J. (2006) · Diabetes · doi:10.2337/db06-0150 · Cited by 315 · see citing works
AMPK: Lessons from transgenic and knockout animals
Viollet, B. (2009) · Frontiers in bioscience · doi:10.2741/3229 · Cited by 314 · see citing works
Contraction signaling to glucose transport in skeletal muscle
Jessen, N., & Goodyear, L. J. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00175.2005 · Cited by 311 · see citing works
Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle
Park, S. H., Gammon, S. R., Knippers, J. D., Paulsen, S. R., Rubink, D. S., & Winder, W. W. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00071.2002 · Cited by 310 · see citing works
Effect of Acute Exercise on AMPK Signaling in Skeletal Muscle of Subjects with Type 2 Diabetes
Sriwijitkamol, A., Coletta, D. K., Wajcberg, E., Balbontin, G. B., Reyna, S. M., Barrientes, J., Eagan, P. A., Jenkinson, C. P., Cersosimo, E., DeFronzo, R. A., et al. (2007) · Diabetes · doi:10.2337/db06-1119 · Cited by 304 · see citing works
AMPK and Exercise: Glucose Uptake and Insulin Sensitivity
O'Neill, H. M. (2013) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2013.37.1.1 · Cited by 295 · see citing works
Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase
Zheng, D., MacLean, P. S., Pohnert, S. C., Knight, J. B., Olson, A. L., Winder, W. W., & Dohm, G. L. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1073 · Cited by 292 · see citing works
Iglesias, M. A., Ye, J.-M., Frangioudakis, G., Saha, A. K., Tomas, E., Ruderman, N. B., Cooney, G. J., & Kraegen, E. W. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2886 · Cited by 290 · see citing works
Self-citationAMPK activity is diminished in tissues of IL-6 knockout mice: the effect of exercise.
Kelly, M., Keller, C., Avilucea, P. R., Keller, P., Luo, Z., Xiang, X., Giralt, M., Hidalgo, J., Saha, A. K., Pedersen, B. K., et al. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.05.188 · Cited by 289 · see citing works
Self-citationThiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues
LeBrasseur, N. K., Kelly, M., Tsao, T.-S., Farmer, S. R., Saha, A. K., Ruderman, N. B., & Tomas, E. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00453.2005 · Cited by 276 · see citing works
Self-citationEffects of α‐AMPK knockout on exercise‐induced gene activation in mouse skeletal muscle
Jørgensen, S. B., Wojtaszewski, J. F. P., Viollet, B., Andreelli, F., Birk, J. B., Hellsten, Y., Schjerling, P., Vaulont, S., Neufer, P. D., Richter, E. A., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-3144fje · Cited by 274 · see citing works
The Role of AMPK in the Regulation of Skeletal Muscle Size, Hypertrophy, and Regeneration
Thomson, D. M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103125 · Cited by 267 · see citing works
Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal
Abu-Elheiga, L. A., Matzuk, M. M., Kordari, P., Oh, W. K., Shaiken, T. E., Gu, Z., & Wakil, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505714102 · Cited by 263 · see citing works
Invited Review: Intracellular signaling in contracting skeletal muscle
Sakamoto, K., & Goodyear, L. J. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00167.2002 · Cited by 260 · see citing works
Turnley, A. M., Stapleton, D., Mann, R. J., Witters, L. A., Kemp, B. E., & Bartlett, P. F. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.721707.x · Cited by 262 · see citing works
Self-citationRole of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise
Jørgensen, S. B., Richter, E. A., & Wojtaszewski, J. F. P. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.109942 · Cited by 261 · see citing works
Glucose, exercise and insulin: emerging concepts
Richter, E. A., Derave, W., & Wojtaszewski, J. F. P. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.t01-2-00313.x · Cited by 258 · see citing works
Zhang, L., Keung, W., Samokhvalov, V., Wang, W. J., & Lopaschuk, G. D. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.09.014 · Cited by 257 · see citing works
Mechanisms Modulating Skeletal Muscle Phenotype
Blaauw, B., Schiaffino, S., & Reggiani, C. (2013) · Comprehensive physiology · doi:10.1002/cphy.c130009 · Cited by 278 · see citing works
Higaki, Y., Hirshman, M. F., FUJII, N. L., & Goodyear, L. J. (2001) · Diabetes · doi:10.2337/diabetes.50.2.241 · Cited by 254 · see citing works
Buhl, E. S., Jessen, N., Pold, R., Ledet, T., Flyvbjerg, A., Pedersen, S. B., Pedersen, O. B., Schmitz, O., & Lund, S. A. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2199 · Cited by 241 · see citing works
Thornton, C., Snowden, M. A., & Carling, D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12443 · Cited by 240 · see citing works
Long-chain fatty acid uptake and FAT/CD36 translocation in heart and skeletal muscle
Koonen, D. P. Y., Glatz, J. F. C., Bonen, A., & Luiken, J. J. F. P. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.08.018 · Cited by 238 · see citing works
Jakobsen, S. N., Hardie, D. G., Morrice, N., & Tornqvist, H. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100483200 · Cited by 238 · see citing works
The Regulation of Fat Metabolism during Aerobic Exercise
Muscella, A., Stefàno, E., Lunetti, P., Capobianco, L., & Marsigliante, S. (2020) · Biomolecules · doi:10.3390/biom10121699 · Cited by 237 · see citing works
Lung adenocarcinoma distally rewires hepatic circadian homeostasis
Masri, S., Papagiannakopoulos, T., Kinouchi, K., Liu, Y., Cervantes, M., Baldi, P., Jacks, T., & Sassone-Corsi, P. (2016) · Cell · doi:10.1016/j.cell.2016.04.039 · Cited by 234 · see citing works
AMP‐activated protein kinase: role in metabolism and therapeutic implications
Schimmack, G., DeFronzo, R. A., & Musi, N. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00561.x · Cited by 229 · see citing works
AMP-activated protein kinase and the regulation of glucose transport
FUJII, N. L., Jessen, N., & Goodyear, L. J. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00207.2006 · Cited by 220 · see citing works
AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle
Musi, N., Hayashi, T., FUJII, N. L., Hirshman, M. F., Witters, L. A., & Goodyear, L. J. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.5.e677 · Cited by 219 · see citing works
Self-citationAMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise
Ruderman, N. B., Park, H., Kaushik, V. K., Dean, D., Constant, S., Prentki, M., & Saha, A. K. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01164.x · Cited by 217 · see citing works
Self-citationJensen, T. E., Rose, A. J., Jørgensen, S. B., Brandt, N., Schjerling, P., Wojtaszewski, J. F. P., & Richter, E. A. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00456.2006 · Cited by 217 · see citing works
p38 MAP Kinase Mediates Apoptosis through Phosphorylation of BimEL at Ser-65
Cai, B., Chang, S. H., Becker, E. B. E., Bonni, A., & Xia, Z. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512627200 · Cited by 210 · see citing works
Dagher, Z., Ruderman, N. B., Tornheim, K., & Ido, Y. (2001) · Circulation Research · doi:10.1161/hh1201.092998 · Cited by 209 · see citing works
Self-citationThe coordination of nuclear and mitochondrial communication during aging and calorie restriction
Finley, L. W. S., & Haigis, M. C. (2009) · Ageing Research Reviews · doi:10.1016/j.arr.2009.03.003 · Cited by 207 · see citing works
Fryer, L. G. D., Foufelle, F., Barnes, K., Baldwin, S. A., Woods, A., & Carling, D. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630167 · Cited by 198 · see citing works
Saha, A. K., Schwarsin, A. J., Roduit, R., Massé, F., Kaushik, V. K., Tornheim, K., Prentki, M., & Ruderman, N. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000291200 · Cited by 194 · see citing works
Self-citationInterleukin-6 Regulation of AMP-Activated Protein Kinase
Ruderman, N. B., Keller, C., Richard, A.-M. T., Saha, A. K., Luo, Z., Xiang, X., Giralt, M., Ritov, V. B., Menshikova, E. V., Kelley, D. E., et al. (2006) · Diabetes · doi:10.2337/db06-s007 · Cited by 190 · see citing works
Self-citationRasmussen, B. B., Holmbäck, U. C., Volpi, E., Morio, B., Paddon‐Jones, D., & Wolfe, R. R. (2002) · Journal of Clinical Investigation · doi:10.1172/jci15715 · Cited by 223 · see citing works
AMP-activated protein kinase phosphorylates transcription factors of the CREB family
Thomson, D. M., Herway, S. T., Fillmore, N., Kim, H., Brown, J. D., Barrow, J. R., & Winder, W. W. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00900.2007 · Cited by 183 · see citing works
Buhl, E. S., Jessen, N., Schmitz, O., Pedersen, S. B., Pedersen, O. B., Holman, G. D., & Lund, S. A. (2001) · Diabetes · doi:10.2337/diabetes.50.1.12 · Cited by 182 · see citing works
The regulation of carbohydrate and fat metabolism during and after exercise
Holloszy, J. O. (1998) · Frontiers in bioscience · doi:10.2741/a342 · Cited by 180 · see citing works
Jørgensen, S. B., Treebak, J. T., Viollet, B., Schjerling, P., Vaulont, S., Wojtaszewski, J. F. P., & Richter, E. A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00243.2006 · Cited by 176 · see citing works
Fujii, N., Hirshman, M. F., Kane, E. M., Ho, R. C., Peter, L. E., Seifert, M. M., & Goodyear, L. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504208200 · Cited by 177 · see citing works
Malonyl-CoA and AMP-activated protein kinase: An expanding partnership
Saha, A. K., & Ruderman, N. B. (2003) · Molecular and Cellular Biochemistry · doi:10.1023/a:1026053302036 · Cited by 177 · see citing works
Self-citationStructure and regulation of acetyl-CoA carboxylase genes of metazoa
BARBER, M. C., Price, N. T., & Travers, M. T. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2004.12.001 · Cited by 176 · see citing works
Dyck, J. R. B., Kudo, N., Barr, A., Davies, S. P., Hardie, D. G., & Lopaschuk, G. D. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00371.x · Cited by 175 · see citing works
Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise
Coven, D. L., Hu, X., Cong, L., Bergeron, R., Shulman, G. I., Hardie, D. G., & Young, L. H. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00171.2003 · Cited by 174 · see citing works
- Authors
- Vavvas, D., Apazidis, A., Saha, A. K., Gamble, J., Patel, A., Kemp, B. E., Witters, L. A., & Ruderman, N. B.
- Affiliations
- Boston University (US)
- Dartmouth College (US)
- St Vincents Institute of Medical Research (AU)
- Corresponding author
- Ruderman, Neil B.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 272
- Issue
- 20
- Pages
- 13255-13261
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1964606633
- Cited by
- 395
- References
- 56
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 15 · 2017: 7 · 2016: 12 · 2015: 12 · 2014: 9 · 2013: 15 · 2012: 9
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Harvard University
- Hebrew University of Jerusalem
- National Institutes of Health (5r01dk019514-35)
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007201, DK-19514, DK-49417, T32-DK07201)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- ACACB, AMPK, skeletal muscle contraction, malonyl-CoA, citrate activation, protein phosphorylation, protein phosphatase 2A, gastrocnemius-soleus muscle, electrical stimulation, enzyme purification, immunoprecipitation
- MeSH terms
- Acetyl-CoA Carboxylase, Animals, Male, Multienzyme Complexes, Muscle Contraction, Protein Kinases, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Muscle, Skeletal, Rats, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
