AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo

Jane Shearer, Patrick T. Fueger, Jeffrey N. Rottman, Deanna P. Bracy, Paul H. Martin, David H. Wasserman

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13 Scopus citations


AMP-activated protein kinase (AMPK) independently increases glucose and long-chain fatty acid (LCFA) utilization in isolated cardiac muscle preparations. Recent studies indicate this may be due to AMPK-induced phosphorylation and activation of nitric oxide synthase (NOS). Given this, the aim of the present study was to assess the effects of AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR; 10 mg·kg-1·min-) on glucose and LCFA utilization in cardiac muscle and to determine the NOS dependence of any observed effects. Catheters were chronically implanted in a carotid artery and jugular vein of Sprague-Dawley rats. After 4 days of recovery, conscious, unrestrained rats were given either water or water containing 1 mg/ml nitro-L-arginine methyl ester (L-NAME) for 2.5 days. After an overnight fast, rats underwent one of four protocols: saline, AICAR, AICAR + L-NAME, or AICAR + Intralipid (20%, 0.02 ml·kg-1·min-1). Glucose was clamped at ∼6.5 mM in all groups, and an intravenous bolus of 2-deoxy-[3H]glucose and [125I]-15-(p-iodophenyl)-3-R,S- methylpentadecanoic acid was administered to obtain indexes of glucose and LCFA uptake and clearance. Despite AMPK activation, as evidenced by acetyl-CoA carboxylase (Ser221) and AMPK phosphorylation (Thr172), AICAR increased cardiac LCFA but not glucose clearance. L-NAME + AICAR established that this effect was not due to NOS activation, and AICAR + Intralipid showed that increased cardiac LCFA clearance was not LCFA-concentration dependent. These results demonstrate that, in vivo, AMPK stimulation increases LCFA but not glucose clearance by a NOS-independent mechanism.

Original languageEnglish (US)
Pages (from-to)E871-E877
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5 50-5
StatePublished - Nov 1 2004


  • AMP-activated protein kinase
  • Carbohydrate
  • Heart
  • Interaction
  • Lipid
  • Long-chain fatty acid
  • Substrate

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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    Shearer, J., Fueger, P. T., Rottman, J. N., Bracy, D. P., Martin, P. H., & Wasserman, D. H. (2004). AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo. American Journal of Physiology - Endocrinology and Metabolism, 287(5 50-5), E871-E877.