Cyclic AMP suppresses the inhibition of glycolysis by alternative oxidizable substrates in the heart

The Journal of Clinical Investigation
C DepreL Hue

Abstract

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. Therefo...Continue Reading

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Citations

Jan 2, 2003·Annals of Nuclear Medicine·Kaoru KobayashiOsamu Inoue
Sep 29, 2011·European Journal of Nuclear Medicine and Molecular Imaging·Jagat Narula, H William Strauss
Oct 20, 2004·Zeitschrift für Kardiologie·K Sroka
Sep 13, 2001·Clinical and Experimental Pharmacology & Physiology·J YoshiokaT Nishimura
Jun 18, 2009·American Journal of Physiology. Endocrinology and Metabolism·Louis Hue, Heinrich Taegtmeyer
Jul 18, 2002·The Journal of Physiology·Jukka KemppainenJuhani Knuuti
May 13, 2005·Chest·Nino StocchettiAnton A van der Plas
Jun 4, 2014·Journal of Applied Biobehavioral Research·Frank J JenkinsDana H Bovbjerg
Oct 18, 2015·Biochimie·Timothy M GriffinLuke I Szweda
Aug 3, 2004·Microscopy Research and Technique·Othon B KotoulasDimitrios J Kondomerkos
Feb 2, 1999·Circulation·C DepreH Taegtmeyer
Dec 6, 2017·Journal of the American Heart Association·Lee B BockusKenneth M Humphries
Sep 29, 2019·The Journal of Biological Chemistry·Maria F NewhardtKenneth M Humphries
Jul 12, 2002·American Journal of Physiology. Endocrinology and Metabolism·Cheol S ChoiJang H Youn
Aug 1, 2016·Journal of the Intensive Care Society·Mohamed M Mohamed, Jon Sturman
Jun 5, 1998·The American Journal of Physiology·C DepreL Hue
Oct 16, 2015·The Journal of Biological Chemistry·Lee B Bockus, Kenneth M Humphries

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