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Am J Physiol Endocrinol Metab 273: E1107-E1112, 1997;
0193-1849/97 $5.00
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Vol. 273, Issue 6, E1107-E1112, December 1997

AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle

G. F. Merrill1, E. J. Kurth2, D. G. Hardie3, and W. W. Winder2

1 Department of Biological Sciences, Rutgers University, New Brunswick, New Jersey 98903; 2 Zoology Department, Brigham Young University, Provo, Utah 84602; and 3 Department of Biochemistry, The University, Dundee DD1 4HN, Scotland, United Kingdom

5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously been reported to be taken up into cells and phosphorylated to form ZMP, an analog of 5'-AMP. This study was designed to determine whether AICAR can activate AMP-activated protein kinase (AMPK) in skeletal muscle with consequent phosphorylation of acetyl-CoA carboxylase (ACC), decrease in malonyl-CoA, and increase in fatty acid oxidation. Rat hindlimbs were perfused with Krebs-Henseleit bicarbonate containing 4% bovine serum albumin, washed bovine red blood cells, 200 µU/ml insulin, and 10 mM glucose with or without AICAR (0.5-2.0 mM). Perfusion with medium containing AICAR was found to activate AMPK in skeletal muscle, inactivate ACC, and decrease malonyl-CoA. Hindlimbs perfused with 2 mM AICAR for 45 min exhibited a 2.8-fold increase in fatty acid oxidation and a significant increase in glucose uptake. No difference was observed in oxygen uptake in AICAR vs. control hindlimb. These results provide evidence that decreases in muscle content of malonyl-CoA can increase the rate of fatty acid oxidation.

acetyl-CoA carboxylase; malonyl-CoA; palmitate oxidation; 5-aminoimidazole-4-carboxamide riboside; ZMP


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Am J Physiol Endocrinol Metab, October 1, 2004; 287(4): E616 - E621.
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 Am. J. Physiol. Endocrinol. Metab.Home page
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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 Am. J. Physiol. Cell Physiol.Home page
H. Yu, N. Fujii, M. F. Hirshman, J. M. Pomerleau, and L. J. Goodyear
Cloning and characterization of mouse 5'-AMP-activated protein kinase {gamma}3 subunit
Am J Physiol Cell Physiol, February 1, 2004; 286(2): C283 - C292.
[Abstract] [Full Text]

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 J. Appl. Physiol.Home page
M. J. Christopher, Z.-P. Chen, C. Rantzau, B. E. Kemp, and F. P. Alford
Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise
J Appl Physiol, October 1, 2003; 95(4): 1523 - 1530.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
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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 Am. J. Physiol. Endocrinol. Metab.Home page
D. L. Coven, X. Hu, L. Cong, R. Bergeron, G. I. Shulman, D. G. Hardie, and L. H. Young
Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise
Am J Physiol Endocrinol Metab, September 1, 2003; 285(3): E629 - E636.
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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
S. L. Longnus, R. B. Wambolt, H. L. Parsons, R. W. Brownsey, and M. F. Allard
5-Aminoimidazole-4-carboxamide 1-beta -D-ribofuranoside (AICAR) stimulates myocardial glycogenolysis by allosteric mechanisms
Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R936 - R944.
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 Am. J. Physiol. Endocrinol. Metab.Home page
J. F. P. Wojtaszewski, C. MacDonald, J. N. Nielsen, Y. Hellsten, D. G. Hardie, B. E. Kemp, B. Kiens, and E. A. Richter
Regulation of 5'AMP-activated protein kinase activity and substrate utilization in exercising human skeletal muscle
Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E813 - E822.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
G. R. Steinberg, J. W. E. Rush, and D. J. Dyck
AMPK expression and phosphorylation are increased in rodent muscle after chronic leptin treatment
Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E648 - E654.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
S. H. Park, S. R. Paulsen, S. R. Gammon, K. J. Mustard, D. G. Hardie, and W. W. Winder
Effects of thyroid state on AMP-activated protein kinase and acetyl-CoA carboxylase expression in muscle
J Appl Physiol, December 1, 2002; 93(6): 2081 - 2088.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
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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 Am. J. Physiol. Endocrinol. Metab.Home page
G. S. Olsen and B. F. Hansen
AMP kinase activation ameliorates insulin resistance induced by free fatty acids in rat skeletal muscle
Am J Physiol Endocrinol Metab, November 1, 2002; 283(5): E965 - E970.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
L. L. Tortorella and P. F. Pilch
C2C12 myocytes lack an insulin-responsive vesicular compartment despite dexamethasone-induced GLUT4 expression
Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E514 - E524.
[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.
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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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 J. Appl. Physiol.Home page
E. O. Ojuka, L. A. Nolte, and J. O. Holloszy
Increased expression of GLUT-4 and hexokinase in rat epitrochlearis muscles exposed to AICAR in vitro
J Appl Physiol, March 1, 2000; 88(3): 1072 - 1075.
[Abstract] [Full Text] [PDF]


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