Metabolism of palmitate in isolated working hearts from spontaneously diabetic "BB" Wistar rats.
Myocardial fatty acid metabolism was studied in spontaneously-diabetic "BB" Wistar rats. The study involved 4 groups: control Wistar rats, nondiabetic littermates of "BB" Wistar rats, insulin-treated diabetic "BB" rats, and diabetic "BB" rats in which insulin treatment was removed 24 hours prior to study (uncontrolled diabetes). Hearts were perfused for 30 minutes as isolated working hearts in perfusate containing 1.2 mM (1-14C)-palmitate bound to 3% albumin, and 11 mM glucose. Palmitate oxidative rates, calculated as micromoles palmitate oxidized per gram dry weight per minute, were significantly decreased in both diabetic groups (0.447 +/- 0.043 and 0.528 +/- 0.038 in uncontrolled diabetic and treated diabetic versus 0.584 +/- 0.032 and 0.629 +/- 0.033 in nondiabetic littermate and control rats, respectively). This decrease was accompanied, however, by a significant decrease in the heart rate of these 2 groups when compared with control or nondiabetic animals. If the decreased heart function in the diabetic animals was accounted for, no decrease in palmitate oxidative rates occurred, suggesting that fatty acid oxidative metabolism is not impaired in the diabetic myocardium. In the uncontrolled diabetic rats, an increased rate of palmitate incorporation into myocardial triglycerides was seen compared with treated diabetic, nondiabetic littermates, and control rats (8.5 +/- 0.3 mumol/g dry wt/30 min versus 4.8 +/- 0.3, 5.9 +/- 0.7, and 5.7 +/- 0.3, respectively). Myocardial levels of coenzyme A were elevated in the uncontrolled diabetic rats compared with all other groups (647 +/- 25 nmol/g dry wt versus 484 +/- 27, 508 +/- 56, and 534 +/- 9, in treated diabetic, nondiabetic, and control rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Lopaschuk
G D
GD
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Tsang
H
H
D000818:Animals; D003065:Coenzyme A / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019308:Palmitic Acid; D010169:Palmitic Acids / Q000378:metabolism*; D051381:Rats; D011913:Rats, Inbred BB; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D007328:Insulin; D010169:Palmitic Acids; D014280:Triglycerides; D019308:Palmitic Acid; D003065:Coenzyme A