Glucose oxidation rates in fatty acid-perfused isolated working hearts from diabetic rats.
The effect of fatty acids and the carnitine palmitoyltransferase I (CPT I) inhibitor, Etomoxir, on myocardial glucose oxidation in diabetes was studied. 14CO2 production from 11 mM [14C]glucose was measured in control or 6-week streptozotocin-diabetic isolated working rat hearts perfused with or without 1.2 mM palmitate (bound to 3% albumin). In control hearts, addition of palmitate to the buffer resulted in a marked reduction (13-fold) in glucose oxidation rates. Glucose oxidation in diabetic rat hearts perfused with palmitate was almost abolished. Even though glucose oxidation rates were low, exogenous palmitate oxidation rates, measured as 14CO2 production from [14C]palmitate, were not increased in diabetic versus control hearts. Addition of the CPT 1 inhibitor, Etomoxir (1.10(-6) M), resulted in a doubling of glucose oxidation rates in both control and diabetic rat hearts, in the presence or absence of palmitate. The effects of Etomoxir on glucose oxidation could not be explained by reduced exogenous palmitate oxidation or decreased levels of citrate. Cardiac function, as measured by the heart rate x peak systolic pressure product, was reduced in diabetic rat hearts. Etomoxir significantly increased heart function in palmitate-perfused hearts from both control and diabetic rats. These data suggest that fatty acids contribute to decreased glucose oxidation and cardiac function in diabetic rat hearts. These effects of fatty acids can be partially reversed with the CPT 1 inhibitor, Etomoxir.
Wall
S R
SR
Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Lopaschuk
G D
GD
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004852:Epoxy Compounds; D005227:Fatty Acids; D010168:Palmitates; D000255:Adenosine Triphosphate; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; C054207:etomoxir