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Research Article Free access | 10.1172/JCI1168
Hormone and Metabolic Research Unit, International Institute of Cellular and Molecular Pathology, and Division of Cardiology, Louvain University Medical School, Brussels, Belgium.
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Hormone and Metabolic Research Unit, International Institute of Cellular and Molecular Pathology, and Division of Cardiology, Louvain University Medical School, Brussels, Belgium.
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Hormone and Metabolic Research Unit, International Institute of Cellular and Molecular Pathology, and Division of Cardiology, Louvain University Medical School, Brussels, Belgium.
Find articles by Deprez, J. in: JCI | PubMed | Google Scholar
Hormone and Metabolic Research Unit, International Institute of Cellular and Molecular Pathology, and Division of Cardiology, Louvain University Medical School, Brussels, Belgium.
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Hormone and Metabolic Research Unit, International Institute of Cellular and Molecular Pathology, and Division of Cardiology, Louvain University Medical School, Brussels, Belgium.
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Published January 15, 1998 - More info
In normoxic conditions, myocardial glucose utilization is inhibited when alternative oxidizable substrates are available. In this work we show that this inhibition is relieved in the presence of cAMP, and we studied the mechanism of this effect. Working rat hearts were perfused with 5.5 mM glucose alone (controls) or together with 5 mM lactate, 5 mM beta-hydroxybutyrate, or 1 mM palmitate. The effects of 0.1 mM chlorophenylthio-cAMP (CPT-cAMP), a cAMP analogue, were studied in each group. Glucose uptake, flux through 6-phosphofructo-1-kinase, and pyruvate dehydrogenase activity were inhibited in hearts perfused with alternative substrates, and addition of CPT-cAMP completely relieved the inhibition. The mechanism by which CPT-cAMP induced a preferential utilization of glucose was related to an increased glucose uptake and glycolysis, and to an activation of phosphorylase, pyruvate dehydrogenase, and 6-phosphofructo-2-kinase, the enzyme responsible for the synthesis of fructose 2,6-bisphosphate, the well-known stimulator of 6-phosphofructo-1-kinase. In vitro phosphorylation of 6-phosphofructo-2-kinase by cAMP-dependent protein kinase increased the Vmax of the enzyme and decreased its sensitivity to the inhibitor citrate. Therefore, in hearts perfused with various oxidizable substrates, cAMP induces a preferential utilization of glucose by a concerted stimulation of glucose transport, glycolysis, glycogen breakdown, and glucose oxidation.