Glycogen turnover during refeeding in the postabsorptive dog: Implications for the estimation of glycogen formation using tracer methods

Recent ¹³C nuclear magnetic resonance (¹³C-NMR) studies in the anesthetized rat and perfused liver suggest that hepatic glycogen is simultaneously synthesized and degraded, even during combined hyperglycemia and hyperinsulinemia. The presence of glycogen turnover would confound efforts to study glycogen repletion with the use of tracer methods during feeding, particularly if the liver is not glycogen-depleted. To ascertain whether glycogen turnover occurs during normal feeding, we measured live uptake of glucose in 10 awake, healthy, postabsorptive dogs with long-term arterial, portal, and hepatic venous catheters before and for 3 hours after a meal of either glucose alone (1.5 g/kg) or glucose supplemented with crystalline amino acids (0.7 g/kg); the meal was labeled with d-[3-³H]glucose and [U-¹⁴C]alanine. Liver glycogen level was measured in biopsies obtained before and at 180 minutes after the meal. The postabsorptive liver glycogen content was 4.3 ± 0.9 g 100g, and net hepatic glucose release averaged 1.8 ± 0.3 mg/min/kg. Over the 3 hours following feeding, the liver took up glucose (0.37 ± 0.14 and 0.33 ± 0.16 g/kg body weight in dogs receiving glucose and glucose with amino acids, respectively). At 3 hours, glycogen synthesis from d-[3-³H]glucose in the two groups averaged 0.24 ± 0.09 and 0.22 ± 0.05 g/kg, or approximately 15% of the ingested glucose load. ¹⁴C-glucose also was found in liver glycogen, demonstrating ongoing hepatic gluconeogenesis. Net hepatic glycogen synthesis averaged only 7 ± 5 and 4 ± 4 g 3h in glucose- and glucose + amino acid-fed dogs, and overall net hepatic glycogen synthesis was inversely related to the basal glycogen content (r = .74, P < .01). We conclude that in the awake dog following either a glucose or a mixed glucose/amino acid meal, (1) there is net uptake of both glucose and gluconeogenic amino acids by the liver, and both substrates are incorporated into newly synthesized liver glycogen; (2) net glycogen synthesis with either meal is inversely related to preexisting glycogen content; and (3) significant turnover of the liver glycogen pool occurs, and this precludes the use of tracer methods to estimate net changes of liver glycogen from the direct and indirect pathway.