The contribution of gluconeogenesis to glycogen repletion during glucose infusion in endotoxemia

Glycogen repletion rates in liver and skeletal muscle were quantitated, and the contribution of gluconeogenesis to hepatic glycogen repletion and glucose output were determined during glucose infusion in hemodynamically stable endotoxemic animals. Four hours after the injection of endotoxin (or saline), rats were infused with 235 μmol/min/kg of glucose (or saline) containing [6-³H]-glucose for up to four additional hours. Glucose infusion increased the plasma glucose concentration, which plateaued between 14 to 17 mmol/L, in the control rats. The glucose concentration of the endotoxin group receiving glucose was consistently greater than in control rats and failed to reach a plateau. The rate of muscle glycogen synthesis was not altered after endotoxin, but hepatic glycogen repletion was decreased by 55%. The percentage of glycogen repletion derived directly from blood glucose in liver and muscle was similar in control and endotoxin-treated rats receiving glucose. Therefore, the direct incorporation of glucose into glycogen appeared to predominate over the contribution by gluconeogenesis. However, gluconeogenesis continued during the glucose infusion in both control and endotoxemic animals. The calculated rate of total gluconeogenesis was 160% higher in the endotoxin glucose-infused rats compared to the control animals receiving glucose. This increase was due primarily to the attenuated suppression of hepatic glucose output in the endotoxin group (52 ± 4%) compared to controls (84 ± 3%). Thus, gluconeogenically derived glucose-6-phosphate appears to be diverted from hepatic glycogen storage to glucose output in endotoxin-treated rats during glucose infusion.