AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle.
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.
Merrill
G F
GF
Department of Biological Sciences, Rutgers University, New Brunswick, New Jersey 98903, USA.
Kurth
E J
EJ
Hardie
D G
DG
Winder
W W
WW
D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000494:pharmacology; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D004912:Erythrocytes / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D019308:Palmitic Acid / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D017207:Rats, Sprague-Dawley; D012263:Ribonucleosides / Q000494:pharmacology*; D012265:Ribonucleotides / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D000227:Adenine Nucleotides; D007328:Insulin; D009097:Multienzyme Complexes; D012263:Ribonucleosides; D012265:Ribonucleotides; D012710:Serum Albumin, Bovine; D019308:Palmitic Acid; D000620:Aminoimidazole Carboxamide; D008316:Malonyl Coenzyme A; C011651:acadesine; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; C031143:AICA ribonucleotide; D005947:Glucose