| Isoproterenol stimulates 5'-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts. | |
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MedLine Citation:
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PMID: 20656883 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Isoproterenol increases phosphorylation of LKB, 5'-AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase (ACC), enzymes involved in regulating fatty acid oxidation. However, inotropic stimulation selectively increases glucose oxidation in adult hearts. In the neonatal heart, fatty acid oxidation becomes a major energy source, while glucose oxidation remains low. This study tested the hypothesis that increased energy demand imposed by isoproterenol originates from fatty acid oxidation, secondary to increased LKB, AMPK, and ACC phosphorylation. Isolated working hearts from 7-day-old rabbits were perfused with Krebs solution (0.4 mM palmitate, 11 mM glucose, 0.5 mM lactate, and 100 mU/l insulin) with or without isoproterenol (300 nM). Isoproterenol increased myocardial O(2) consumption (in J·g dry wt(-1)·min(-1); 11.0 ± 1.4, n = 8 vs. 7.5 ± 0.8, n = 6, P < 0.05), and the phosphorylation of LKB (in arbitrary density units; 0.87 ± 0.09, n = 6 vs. 0.59 ± 0.08, n = 6, P < 0.05), AMPK (0.82 ± 0.08, n = 6 vs. 0.51 ± 0.06, n = 6, P < 0.05), and ACC-β (1.47 ± 0.14, n = 6 vs. 0.97 ± 0.07, n = 6, P < 0.05), with a concomitant decrease in malonyl-CoA levels (in nmol/g dry wt; 0.9 ± 0.9, n = 8 vs. 7.5 ± 1.3, n = 8, P < 0.05) and increase in palmitate oxidation (in nmol·g dry wt(-1)·min(-1); 272 ± 45, n = 8 vs. 114 ± 9, n = 6, P < 0.05). Glucose and lactate oxidation were increased (in nmol·g dry wt(-1)·min(-1); 253 ± 75, n = 8 vs. 63 ± 15, n = 9, P < 0.05 and 246 ± 43, n = 8 vs. 82 ± 11, n = 6, P < 0.05, respectively), independent of alterations in pyruvate dehydrogenase phosphorylation, but occurred secondary to a decrease in acetyl-CoA content and acetyl-CoA-to-free CoA ratio. As acetyl-CoA levels decrease in response to isoproterenol, despite an acceleration of the rates of palmitate and carbohydrate oxidation, these data suggest net rates of acetyl-CoA utilization exceed the net rates of acetyl-CoA generation. |
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Authors:
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Jagdip S Jaswal; Chad R Lund; Wendy Keung; Donna L Beker; Ivan M Rebeyka; Gary D Lopaschuk |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-07-23 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-04 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1135-45 Citation Subset: IM |
Affiliation:
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Department of Pediatrics, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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AMP-Activated Protein Kinases
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metabolism* Acetyl Coenzyme A / metabolism Acetyl-CoA Carboxylase / metabolism Adenosine Triphosphate / metabolism Animals Animals, Newborn / metabolism* Cardiotonic Agents / pharmacology* Fatty Acids / metabolism* Female Glucose / metabolism Isoproterenol / pharmacology* Lactates / metabolism Male Models, Animal Myocardium / metabolism* Oxidation-Reduction / drug effects Oxygen Consumption / drug effects Phosphorylation / drug effects Protein-Serine-Threonine Kinases / metabolism Rabbits Ventricular Function, Left / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Fatty Acids; 0/Lactates; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 72-89-9/Acetyl Coenzyme A; 7683-59-2/Isoproterenol; EC 2.7.11.1/AMP-Activated Protein Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 6.4.1.2/Acetyl-CoA Carboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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