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 mumol/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.

Glycogen synthase and phosphorylase activities during glycogen repletion in endotoxemic rats.

The activities of glycogen synthase and glycogen phosphorylase were quantitated in liver and skeletal muscle removed following glucose infusion in hemodynamically stable endotoxin-treated rats. Four hours after the IV injection of endotoxin or saline, rats were infused with 235 mumole/min/kg of glucose or saline for up to 4 additional hr. Saline-infused endotoxemic rats had lower basal glycogen content in muscle and liver, which was associated with an increased phosphorylase a activity in both tissues compared to controls. During the glucose infusion, the rate of glycogen repletion in muscle was similar in the two groups. Skeletal muscle phosphorylase a and glycogen synthase I & D activities were elevated above control values in endotoxemia, while glycogen synthase I activity remain unchanged. These changes in the activity of muscle phosphorylase and synthase are consistent with an increased flux of carbon into and out of glycogen and a normal rate of net glycogen synthesis during glucose infusion in endotoxin-treated rats. In contrast to muscle, hepatic glycogen synthesis by endotoxemic animals was reduced compared to glucose-infused controls. Hepatic glycogen repletion in control animals appeared to be mediated primarily by a glucose-induced suppression of phosphorylase a activity rather than an increased glycogen synthase activity. Glucose infusion failed to decrease phosphorylase a activity in endotoxin-treated rats, which may be causally related to the impaired ability of these animals to replete liver glycogen.