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J Appl Physiol 71: 1302-1308, 1991;
8750-7587/91 $5.00
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Journal of Applied Physiology, Vol 71, Issue 4 1302-1308, Copyright © 1991 by American Physiological Society

ARTICLES

Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat

G. D. Lopaschuk and J. C. Russell
Department of Pediatrics, University of Alberta, Edmonton, Canada.

Alterations in myocardial energy substrate utilization contribute to the development of cardiomyopathic changes in insulin-dependent and non-insulin-dependent diabetic rats. Energy substrate utilization and contractile function, however, have not been characterized in insulin-resistant diabetes. In this study, we studied these parameters in the insulin-resistant obese JCR:LA-cp rat homozygous for the corpulent gene (cp/cp). Homozygous (+/+) or heterozygous (+/cp) lean non-insulin-resistant rats were used as controls. Isolated working hearts from cp/cp and lean control rats were perfused with Krebs-Henseleit buffer containing either 11 mM [U-14C]glucose and 0.4 mM palmitate or 11 mM glucose and 0.4 mM [1-14C]palmitate. Unlike control hearts, hearts from cp/cp rats were found to require high doses of insulin and Ca2+ concentrations of less than or equal to 1.75 mM to maintain mechanical function. In the presence of 2,000 microU/ml insulin, contractile function from cp/cp rat hearts was not depressed in the presence of either 1.25 or 1.75 mM Ca2+. Steady-state glucose oxidation rates in hearts perfused with 1.25 mM Ca2+ and 2,000 microU/ml insulin were 811 +/- 86 (SE) and 612 +/- 51 nmol.min-1.g dry wt-1 in cp/cp and control rats, respectively. Palmitate oxidation was 307 +/- 47 and 307 +/- 47 nmol.min-1.g dry wt-1 in cp/cp and lean control hearts, respectively. Under these perfusion conditions, 40% of myocardial ATP production was derived from glucose, whereas 60% was derived from palmitate in both cp/cp and control rats.(ABSTRACT TRUNCATED AT 250 WORDS)


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