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

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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
Volume287
Issue number5 50-5
DOIs
StatePublished - Nov 1 2004

Keywords

  • 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. https://doi.org/10.1152/ajpendo.00125.2004