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1 Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
5-Amino-4-imidazolecarboxamide riboside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), acutely stimulates glucose uptake and fatty acid (FA) oxidation in skeletal muscle. However, it is not fully understood whether AICAR-induced changes in glucose oxidation are secondary to changes in FA oxidation (i.e. glucose fatty acid cycle), or what role AMPK may be playing in the regulation of intramuscular triacylglycerol (TAG) esterification and hydrolysis. We examined the acute (60 min) effects of AICAR (2 mM) on FA metabolism, glucose oxidation and pyruvate dehydrogenase (PDH) activation in isolated resting rat soleus muscle strips exposed to two different FA concentrations (low fatty acid, LFA, 0.2 mM; high fatty acid, HFA, 1 mM). AICAR significantly increased AMPK 
2 activity (+192%; P < 0.05) over 60 min, and simultaneously increased both FA (LFA: +33%, P < 0.05; HFA: +36%, P < 0.05) and glucose (LFA: +105%, P < 0.05; HFA: +170, P < 0.001) oxidation regardless of FA availability. While there were no changes in TAG esterification, AICAR did increase the ratio of FA partitioned to oxidation relative to TAG esterification (LFA: +15%, P < 0.05; HFA: +49%, P < 0.05). AICAR had no effect on endogenous TAG hydrolysis and oxidation in resting soleus. The stimulation of glucose oxidation with AICAR was associated with an increase in PDH activation (+126%; P < 0.05) but was without effect on pyruvate, an allosteric activator of the PDH complex, suggesting that AMPK may stimulate PDH directly. In conclusion, AMPK appears to be an important regulator of both FA metabolism and glucose oxidation in resting skeletal muscle.
(Received 20 December 2004;
accepted after revision 14 March 2005;
first published online 17 March 2005)
Corresponding author A. C. Smith: Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada, N1G 2W1. Email: asmith09{at}uoguelph.ca
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