Aica riboside increases amp-activated protein kinase, fatty acid
oxidation and glucose uptake in rat muscle .
Merrill, G. F., E. J. Kurth, D. G. Hardie, and W. W. Winder.
Department of Biological Sciences, Rutgers University, New
Brunswick, NJ 98903, Zoology Department, Brigham Young University,
Provo, Utah 84602, Department of Biochemistry, The University, Dundee
DD1 4HN, Scotland
APStracts 4:0197E, 1997.
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR) has previously
been reported to be taken up into cells and phosphorylated to form
ZMP, an analogue of 5'-AMP. This study was designed to determine
whether AICAR can activate AMP-activated protein kinase 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 (KHB)
containing 4% bovine serum albumin, washed bovine red cells, 200
[mu]U/ml insulin, 10 mM glucose +/- 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.
Received 25 June 1997; accepted in final form 4 September 1997.
APS Manuscript Number E297-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 October 1997