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Am J Physiol Endocrinol Metab 270: E299-E304, 1996;
0193-1849/96 $5.00
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AJP - Endocrinology and Metabolism, Vol 270, Issue 2 E299-E304, Copyright © 1996 by American Physiological Society

ARTICLES

Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise

W. W. Winder and D. G. Hardie
Zoology Department, Brigham Young University, Provo, Utah 84602, USA.

Malonyl-CoA, an inhibitor of fatty acid oxidation in skeletal muscle mitochondria, decreases in rat skeletal muscle during exercise or in response to electrical stimulation. Regulation of rat skeletal muscle acetyl-CoA carboxylase (ACC), the enzyme that synthesizes malonyl-CoA, was studied in vitro and in vivo. Avidin-Sepharose affinity-purified ACC from hindlimb skeletal muscle was phosphorylated by purified liver AMP-activated protein kinase with a concurrent decrease in ACC activity. AMP-activated protein kinase was quantitated in resuspended ammonium sulfate precipitates of the fast-twitch red (type IIa fibers) region of the quadriceps muscle. Rats running on a treadmill at 21 m/min up a 15% grade show a 2.4-fold activation of AMP-activated protein kinase concurrently with a marked decrease in ACC activity in the resuspended ammonium sulfate precipitates at all citrate concentrations ranging from 0 to 20 mM. Malonyl-CoA decreased from a resting value of 1.85 +/- 0.29 to 0.50 +/- 0.09 nmol/g in red quadriceps muscle after 30 min of treadmill running. The activation of the AMP-activated protein kinase with consequent phosphorylation and inactivation of ACC may be one of the primary events in the control of malonyl-CoA and hence fatty acid oxidation during exercise.


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E. Tomas, A. Zorzano, and N. B. Ruderman
Exercise Effects on Muscle Insulin Signaling and Action: Exercise and insulin signaling: a historical perspective
J Appl Physiol, August 1, 2002; 93(2): 765 - 772.
[Abstract] [Full Text] [PDF]

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S. A. Hawley, A. E. Gadalla, G. S. Olsen, and D. G. Hardie
The Antidiabetic Drug Metformin Activates the AMP-Activated Protein Kinase Cascade via an Adenine Nucleotide-Independent Mechanism
Diabetes, August 1, 2002; 51(8): 2420 - 2425.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
F. W. Booth, M. V. Chakravarthy, S. E. Gordon, and E. E. Spangenburg
Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy
J Appl Physiol, July 1, 2002; 93(1): 3 - 30.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
K. Sakamoto and L. J. Goodyear
Exercise Effects on Muscle Insulin Signaling and Action: Invited Review: Intracellular signaling in contracting skeletal muscle
J Appl Physiol, July 1, 2002; 93(1): 369 - 383.
[Abstract] [Full Text] [PDF]

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E. S. Buhl, N. Jessen, R. Pold, T. Ledet, A. Flyvbjerg, S. B. Pedersen, O. Pedersen, O. Schmitz, and S. Lund
Long-Term AICAR Administration Reduces Metabolic Disturbances and Lowers Blood Pressure in Rats Displaying Features of the Insulin Resistance Syndrome
Diabetes, July 1, 2002; 51(7): 2199 - 2206.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
P. E. Durante, K. J. Mustard, S.-H. Park, W. W. Winder, and D. G. Hardie
Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles
Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E178 - E186.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
S. H. Park, S. R. Gammon, J. D. Knippers, S. R. Paulsen, D. S. Rubink, and W. W. Winder
Phosphorylation-activity relationships of AMPK and acetyl-CoA carboxylase in muscle
J Appl Physiol, June 1, 2002; 92(6): 2475 - 2482.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
H. Sakoda, T. Ogihara, M. Anai, M. Fujishiro, H. Ono, Y. Onishi, H. Katagiri, M. Abe, Y. Fukushima, N. Shojima, et al.
Activation of AMPK is essential for AICAR-induced glucose uptake by skeletal muscle but not adipocytes
Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1239 - E1244.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
H. Ai, J. Ihlemann, Y. Hellsten, H. P. M. M. Lauritzen, D. G. Hardie, H. Galbo, and T. Ploug
Effect of fiber type and nutritional state on AICAR- and contraction-stimulated glucose transport in rat muscle
Am J Physiol Endocrinol Metab, June 1, 2002; 282(6): E1291 - E1300.
[Abstract] [Full Text] [PDF]

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J. F.P. Wojtaszewski, S. B. Jorgensen, Y. Hellsten, D. G. Hardie, and E. A. Richter
Glycogen-Dependent Effects of 5-Aminoimidazole-4-Carboxamide (AICA)-Riboside on AMP-Activated Protein Kinase and Glycogen Synthase Activities in RatSkeletal Muscle
Diabetes, February 1, 2002; 51(2): 284 - 292.
[Abstract] [Full Text] [PDF]

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J. D. McGarry
Banting Lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes
Diabetes, January 1, 2002; 51(1): 7 - 18.
[Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
J. S. Fisher, J. Gao, D.-H. Han, J. O. Holloszy, and L. A. Nolte
Activation of AMP kinase enhances sensitivity of muscle glucose transport to insulin
Am J Physiol Endocrinol Metab, January 1, 2002; 282(1): E18 - E23.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. N. Jakobsen, D. G. Hardie, N. Morrice, and H. E. Tornqvist
5'-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside
J. Biol. Chem., December 7, 2001; 276(50): 46912 - 46916.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
R. Bergeron, J. M. Ren, K. S. Cadman, I. K. Moore, P. Perret, M. Pypaert, L. H. Young, C. F. Semenkovich, and G. I. Shulman
Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis
Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1340 - E1346.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
R. Somwar, W. Niu, D. Y. Kim, G. Sweeney, V. K. Randhawa, C. Huang, T. Ramlal, and A. Klip
Differential Effects of Phosphatidylinositol 3-Kinase Inhibition on Intracellular Signals Regulating GLUT4 Translocation and Glucose Transport
J. Biol. Chem., November 30, 2001; 276(49): 46079 - 46087.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
S. R. Paulsen, D. S. Rubink, and W. W. Winder
AMP-activated protein kinase activation prevents denervation-induced decline in gastrocnemius GLUT-4
J Appl Physiol, November 1, 2001; 91(5): 2102 - 2108.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
W. W. Winder
Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle
J Appl Physiol, September 1, 2001; 91(3): 1017 - 1028.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
D. Zheng, P. S. MacLean, S. C. Pohnert, J. B. Knight, A. L. Olson, W. W. Winder, and G. L. Dohm
Regulation of muscle GLUT-4 transcription by AMP-activated protein kinase
J Appl Physiol, September 1, 2001; 91(3): 1073 - 1083.
[Abstract] [Full Text] [PDF]

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N. Musi, N. Fujii, M. F. Hirshman, I. Ekberg, S. Fröberg, O. Ljungqvist, A. Thorell, and L. J. Goodyear
AMP-Activated Protein Kinase (AMPK) Is Activated in Muscle of Subjects With Type 2 Diabetes During Exercise
Diabetes, May 1, 2001; 50(5): 921 - 927.
[Abstract] [Full Text]

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 Am. J. Physiol. Endocrinol. Metab.Home page
N. Musi, T. Hayashi, N. Fujii, M. F. Hirshman, L. A. Witters, and L. J. Goodyear
AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle
Am J Physiol Endocrinol Metab, May 1, 2001; 280(5): E677 - E684.
[Abstract] [Full Text] [PDF]

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R. Bergeron, S. F. Previs, G. W. Cline, P. Perret, R. R. Russell III, L. H. Young, and G. I. Shulman
Effect of 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside Infusion on In Vivo Glucose and Lipid Metabolism in Lean and Obese Zucker Rats
Diabetes, May 1, 2001; 50(5): 1076 - 1082.
[Abstract] [Full Text]

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L. Abu-Elheiga, M. M. Matzuk, K. A. H. Abo-Hashema, and S. J. Wakil
Continuous Fatty Acid Oxidation and Reduced Fat Storage in Mice Lacking Acetyl-CoA Carboxylase 2
Science, March 30, 2001; 291(5513): 2613 - 2616.
[Abstract] [Full Text]

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E. S. Buhl, N. Jessen, O. Schmitz, S. B. Pedersen, O. Pedersen, G. D. Holman, and S. Lund
Chronic Treatment With 5-Aminoimidazole-4-Carboxamide-1-{beta}-D-Ribofuranoside Increases Insulin-Stimulated Glucose Uptake and GLUT4 Translocation in Rat Skeletal Muscles in a Fiber Type--Specific Manner
Diabetes, January 1, 2001; 50(1): 12 - 17.
[Abstract] [Full Text]

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 J. Appl. Physiol.Home page
W. W. Winder and B. F. Holmes
Insulin stimulation of glucose uptake fails to decrease palmitate oxidation in muscle if AMPK is activated
J Appl Physiol, December 1, 2000; 89(6): 2430 - 2437.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
K. Kawanaka, L. A. Nolte, D.-H. Han, P. A. Hansen, and J. O. Holloszy
Mechanisms underlying impaired GLUT-4 translocation in glycogen-supercompensated muscles of exercised rats
Am J Physiol Endocrinol Metab, December 1, 2000; 279(6): E1311 - E1318.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
J. Ihlemann, T. Ploug, Y. Hellsten, and H. Galbo
Effect of stimulation frequency on contraction-induced glucose transport in rat skeletal muscle
Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E862 - E867.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
W. W. Winder, B. F. Holmes, D. S. Rubink, E. B. Jensen, M. Chen, and J. O. Holloszy
Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle
J Appl Physiol, June 1, 2000; 88(6): 2219 - 2226.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
B. F. Holmes, E. J. Kurth-Kraczek, and W. W. Winder
Chronic activation of 5'-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle
J Appl Physiol, November 1, 1999; 87(5): 1990 - 1995.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
J. Ihlemann, T. Ploug, Y. Hellsten, and H. Galbo
Effect of tension on contraction-induced glucose transport in rat skeletal muscle
Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E208 - E214.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Heart Circ. Physiol.Home page
R. R. Russell III, R. Bergeron, G. I. Shulman, and L. H. Young
Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR
Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H643 - H649.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
W. W. Winder and D. G. Hardie
AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes
Am J Physiol Endocrinol Metab, July 1, 1999; 277(1): E1 - E10.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
A. K. Saha, D. R. Laybutt, D. Dean, D. Vavvas, E. Sebokova, B. Ellis, I. Klimes, E. W. Kraegen, E. Shafrir, and N. B. Ruderman
Cytosolic citrate and malonyl-CoA regulation in rat muscle in vivo
Am J Physiol Endocrinol Metab, June 1, 1999; 276(6): E1030 - E1037.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
R. Bergeron, R. R. Russell III, L. H. Young, J.-M. Ren, M. Marcucci, A. Lee, and G. I. Shulman
Effect of AMPK activation on muscle glucose metabolism in conscious rats
Am J Physiol Endocrinol Metab, May 1, 1999; 276(5): E938 - E944.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
C. L. Carlson and W. W. Winder
Liver AMP-activated protein kinase and acetyl-CoA carboxylase during and after exercise
J Appl Physiol, February 1, 1999; 86(2): 669 - 674.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
N. B. Ruderman, A. K. Saha, D. Vavvas, and L. A. Witters
Malonyl-CoA, fuel sensing, and insulin resistance
Am J Physiol Endocrinol Metab, January 1, 1999; 276(1): E1 - E18.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
B. B. Rasmussen, C. R. Hancock, and W. W. Winder
Postexercise recovery of skeletal muscle malonyl-CoA, acetyl-CoA carboxylase, and AMP-activated protein kinase
J Appl Physiol, November 1, 1998; 85(5): 1629 - 1634.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
G. F. Merrill, E. J. Kurth, B. B. Rasmussen, and W. W. Winder
Influence of malonyl-CoA and palmitate concentration on rate of palmitate oxidation in rat muscle
J Appl Physiol, November 1, 1998; 85(5): 1909 - 1914.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
L. M. Odland, R. A. Howlett, G. J. F. Heigenhauser, E. Hultman, and L. L. Spriet
Skeletal muscle malonyl-CoA content at the onset of exercise at varying power outputs in humans
Am J Physiol Endocrinol Metab, June 1, 1998; 274(6): E1080 - E1085.
[Abstract] [Full Text] [PDF]


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