Abstract
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 microU/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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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AMP-Activated Protein Kinases
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Acetyl-CoA Carboxylase / metabolism*
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Adenine Nucleotides / pharmacology
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Aminoimidazole Carboxamide / analogs & derivatives*
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Cattle
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Enzyme Activation
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Erythrocytes / physiology*
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Glucose / metabolism*
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Hindlimb
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Insulin / pharmacology
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Kinetics
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Male
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Malonyl Coenzyme A / metabolism*
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Multienzyme Complexes / metabolism*
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Muscle, Skeletal / blood supply
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Muscle, Skeletal / drug effects
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Muscle, Skeletal / physiology*
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Palmitic Acid / metabolism*
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Phosphorylation
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Protein Kinases / metabolism*
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Protein Serine-Threonine Kinases*
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Rats
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Rats, Sprague-Dawley
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Ribonucleosides / pharmacology*
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Ribonucleotides / pharmacology
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Serum Albumin, Bovine / pharmacology
Substances
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Adenine Nucleotides
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Insulin
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Multienzyme Complexes
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Ribonucleosides
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Ribonucleotides
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Serum Albumin, Bovine
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Palmitic Acid
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Aminoimidazole Carboxamide
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Malonyl Coenzyme A
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acadesine
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Protein Kinases
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Protein Serine-Threonine Kinases
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AMP-Activated Protein Kinases
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Acetyl-CoA Carboxylase
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AICA ribonucleotide
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Glucose