Acute insulin withdrawal from diabetic BB rats decreases myocardial glycolysis during low-flow ischemia.
We have previously demonstrated that withdrawal of insulin treatment from BB diabetic rats for a 24-hour period will increase the failure rate of hearts subjected to low-flow ischemia. The purpose of this study was to determine if this increased severity of ischemia was related to a decrease in glycolytic rates during ischemia. Two groups of insulin-dependent diabetic BB Wistar rats were used; in one group, insulin treatment was withheld from rats 24 hours prior to study (uncontrolled), while in the second group, the daily insulin injection was not withheld (insulin-treated). Isolated working hearts obtained from these animals were perfused with 30 mmol/L (2-3H/U-14C)-glucose and 1.2 mmol/L palmitate, at an 11.5 mm Hg left atrial preload and 80 mm Hg aortic afterload. Hearts were subjected to a 15-minute aerobic perfusion followed by 60 minutes of low-flow ischemia (coronary flow, 0.5 mL/min). Under aerobic conditions, steady-state glucose oxidation rates (measured as 14CO2 production) were decreased in the uncontrolled group compared with the insulin-treated group (85.3 +/- 21.5 v 406.2 +/- 120.1 nmol/min/g dry weight, respectively; P less than .05). Steady-state glycolytic rates (measured as 3H2O production) were also decreased in the uncontrolled group compared with the insulin-treated group (1.73 +/- 0.30 v 5.57 +/- 1.26 mumol/min/g dry weight, respectively; P less than .05). During low-flow ischemia, glucose-oxidation rates markedly decreased in both groups (23.9 +/- 8.7 and 38.3 +/- 25.2 nmol/min/g dry weight in the uncontrolled and insulin-treated diabetic rats, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Broderick
T L
TL
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Barr
R L
RL
Quinney
H A
HA
Lopaschuk
G D
GD
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D066298:In Vitro Techniques; D007328:Insulin / Q000627:therapeutic use*; D007511:Ischemia; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011913:Rats, Inbred BB; D015424:Reperfusion
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005947:Glucose