Document Detail

Effects of phosphodiesterase inhibitors on glucose utilization in isolated cardiac myocytes.
MedLine Citation:
PMID:  9546639     Owner:  NLM     Status:  MEDLINE    
The phosphodiesterase (PDE) inhibitor, enoximone, enhances the oxidation of fatty acids in cardiac myocytes. Since carbohydrate oxidation is tightly coupled and inversely related in cardiac tissue to fatty acid oxidation, this study was designed to investigate enoximone's effects on glucose metabolism in the heart. To determine if enoximone alters this reciprocal relationship, the effects of enoximone on [U-14C]glucose and [2-14C]pyruvate oxidation were determined in isolated cardiac myocytes. The effect of PDE inhibitors was also examined on pyruvate dehydrogenase complex (PDH) activity, a key component of oxidative glucose metabolism. Two PDE inhibitors, enoximone and milrinone, decreased PDH activity by 69 and 64%, respectively at 0.5 mM. This inhibition of PDH activity by enoximone was completely reversed after removing enoximone from the myocyte medium. PDH activity was unaffected by agents which alter cyclic nucleotide signaling: cGMP, dibutyryl cyclic AMP, and AMP. The effect of enoximone on [2-14C]pyruvate oxidation was similar to that on PDH. Interestingly, the oxidation of glucose was decreased 35% by 0.5 mM enoximone. In isolated rat heart mitochondria (RHM), enoximone decreased PDH activity by 37%. These studies suggest that PDE inhibitors decrease carbohydrate utilization by inhibiting the PDH complex in the heart. The inhibition of PDH by PDE inhibitors appears unrelated to their effects on cAMP or cGMP. This inhibition of PDH by PDE inhibitors may occur, at least in part, secondary to stimulating fatty acid oxidation.
S Abdel-aleem; M K El Awadi; W A Zarouk; D Taylor; J E Lowe
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  180     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-05-21     Completed Date:  1998-05-21     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  129-35     Citation Subset:  IM    
Duke University Medical Center, Department of Surgery, Durham, North Carolina 27710, USA.
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MeSH Terms
Carbohydrate Metabolism
Enoximone / pharmacology
Glucose / metabolism*
Heart / drug effects
Myocardium / metabolism*
Phosphodiesterase Inhibitors / pharmacology*
Pyruvate Dehydrogenase Complex / metabolism
Rats, Sprague-Dawley
Reg. No./Substance:
0/Phosphodiesterase Inhibitors; 0/Pyruvate Dehydrogenase Complex; 50-99-7/Glucose; 77671-31-9/Enoximone

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