Lipid-mediated impairment of normal energy metabolism in the isolated perfused diabetic rat heart studied by phosphorus-31 NMR and chemical extraction |
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| Authors: | Galen M. Pieper J.M. Salhany Wallace J. Murray Shao T. Wu Robert S. Eliot |
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| Affiliation: | 1. Department of Preventive and Stress Medicine, 3012 Poynter Hall, Omaha, NE 68105 U.S.A.;2. Department of Biomedicinal Chemistry, University of Nebraska Medical Center, 42nd and Dewey Ave., Omaha, NE 68105 U.S.A.;3. VA Medical Center, Omaha, NE 68105 U.S.A. |
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| Abstract: | The relationship between extracellular palmitate and the accumulation of long-chain fatty-acyl coenzyme A with that of high-energy phosphate metabolism was investigated in the isolated perfused diabetic rat heart. Hearts were perfused with a glucose/albumin buffer supplemented with 0, 0.5, 1.2 or 2.0 mM palmitate. 31P-NMR was used to analyze phosphocreatine and ATP metabolism during 1 h of constant-flow recirculation perfusion. At the end of perfusion, frozen samples were taken for chemical analysis of high-energy phosphates and the free and acylated fractions of coenzyme A and carnitine. Perfusion of diabetic hearts with palmitate, unlike control hearts, caused a time-dependent and concentration-dependent reduction in ATP, despite normal and constant phosphocreatine. Concentrations of acid-soluble coenzyme A, long-chain-acyl coenzyme A and total tissue coenzyme A were elevated in palmitate-perfused diabetic hearts, while the total tissue carnitine pool was decreased. Increases in long-chain-acyl coenzyme A correlated with the reduction in myocardial ATP. This reduction in ATP could not be adequately explained by alterations in heart rate, perfusion pressure or vascular resistance. |
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| Keywords: | Long-chain acyl-CoA Carnitine Diabetes ATP Phosphocreatine (Rat heart) |
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