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

Am J Physiol. 1997 Dec;273(6):E1107-12. doi: 10.1152/ajpendo.1997.273.6.E1107.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase / metabolism*
  • Adenine Nucleotides / pharmacology
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Cattle
  • Enzyme Activation
  • Erythrocytes / physiology*
  • Glucose / metabolism*
  • Hindlimb
  • Insulin / pharmacology
  • Kinetics
  • Male
  • Malonyl Coenzyme A / metabolism*
  • Multienzyme Complexes / metabolism*
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiology*
  • Palmitic Acid / metabolism*
  • Phosphorylation
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleosides / pharmacology*
  • Ribonucleotides / pharmacology
  • Serum Albumin, Bovine / pharmacology

Substances

  • Adenine Nucleotides
  • Insulin
  • Multienzyme Complexes
  • Ribonucleosides
  • Ribonucleotides
  • Serum Albumin, Bovine
  • Palmitic Acid
  • Aminoimidazole Carboxamide
  • Malonyl Coenzyme A
  • acadesine
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase
  • AICA ribonucleotide
  • Glucose