Contribution of Glycogen to Aerobic Myocardial Glucose Utilization

Abstract

Background We determined glycogen turnover and the contribution of glycogen as a source of glucose for aerobic myocardial glycolysis and glucose oxidation in parallel series of isolated, working rat hearts subjected to pulse-chase perfusions. Methods and Results Myocardial glycogen of isolated, working rat hearts was radiolabeled, after 30 minutes of substrate-free glycogen depletion, by perfusion for 60 minutes with buffer designed to stimulate resynthesis of glycogen (1.2 mmol/L palmitate, 11 mmol/L [U- 14 C]- or [5- 3 H]-glucose, 0.5 mmol/L lactate, and 100 μU/mL insulin). Rates of glucose oxidation ( 14 CO 2 production) and glycolysis ( 3 H 2 O production) were then measured by perfusing the hearts for 40 minutes with buffer designed to simulate physiological conditions (0.4 mmol/L palmitate, 0.5 mmol/L lactate, 11 mmol/L [5- 3 H]- or [U- 14 C]-glucose, 100 μU/mL insulin) containing radiolabeled glucose different from that used during resynthesis. During the chase perfusion, rates of glycolysis and glucose oxidation from exogenous glucose were significantly greater than those from endogenous glycogen. Nevertheless, glycogen contributed significantly to myocardial energy production (41% of the overall ATP produced from glucose), and a significantly greater fraction of the glucose from glycogen that passed through glycolysis was oxidized (>50%) compared with the fraction oxidized from exogenous glucose (<20%, P <.05). Myocardial glycogen was simultaneously synthesized and degraded (ie, glycogen turnover) during the chase perfusion, despite net glycogenolysis. Furthermore, enrichment of labeled glucose in glycogen at the end of the chase perfusion, when corrected for newly synthesized glycogen, did not differ from that at the end of the labeling period. Conclusions Thus, glycogen contributes significantly to aerobic myocardial glucose use under these experimental conditions, and the glucose derived from glycogen is oxidized preferentially compared with exogenous glucose. Additionally, substantial myocardial glycogen turnover occurs, and the manner in which glycogen is degraded does not fit the ordered hypothesis of “last glucose on, first glucose off.”