Myocardial function and energy substrate metabolism in the insulin-resistant JCR:LA corpulent rat.
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)
Lopaschuk
G D
GD
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Russell
J C
JC
D000818:Animals; D001835:Body Weight / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D009929:Organ Size / Q000502:physiology; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010168:Palmitates; D005947:Glucose