Nonglucose substrates increase glycogen synthesis in vivo in dog heart

The effects of circulating nonglucose substrates on insulin-stimulated cardiac glycogen synthesis were studied in the dog heart in vivo using 13C-nuclear magnetic resonance (-NMR) and arteriovenous difference techniques. [1-13C]glycogen was monitored in hearts during an intravenous infusion of 20 mU/min insulin and glucose while [1-13C]glucose (10 mg/min) was infused into the left anterior descending coronary artery. When 1 mmol/min of lactate, pyruvate, or beta-hydroxybutyrate was added to the venous infusion, the measured rate of glycogen synthesis was increased, on average, sixfold. It was not increased further after a subsequent 10-min infusion of 5 micrograms/min epinephrine. Lactate extraction increased from 0.18 +/- 0.05 to 0.62 +/- 0.11 mumol.min-1.g wet wt-1 during lactate infusion, whereas glucose extraction did not change significantly (0.15 +/- 0.05 mumol.min-1.g wet wt-1 at 45 min of insulin and glucose infusion to 0.09 +/- 0.02 mumol.min-1.g wet wt-1 at 45 min of the lactate infusion). Therefore, the uptake and oxidation of circulating nonglucose substrates redirects the fate of extracted glucose from glycolysis to glycogen synthesis in the dog heart in vivo.