Glucose dyshomeostasis is a common and life-threatening sign of endotoxic shock in the newborn. In this study, liver gluconeogenesis was evaluated in 10-day-old rats with endotoxic shock using the isolated perfused liver. Phosphoenolpyruvate carboxykinase (PEPCK) activity and PEPCK mRNA abundance were measured to confirm altered gluconeogenesis. Glucose disposal was also evaluated by a glucose tolerance test. Twenty-four-hour-fasted rats were studied to enhance gluconeogenesis and decrease glucose disposal. Rats received an intraperitoneal (IP) injection as follows: group 1 (fed-saline), 0.2 mL saline in fed rats; group 2 (fed-LPS), 0.1 mg/kg Salmonella enteritidis lipopolysaccharide (LPS) in fed rats; group 3 (fasted-saline), 0.2 mL saline in fasted rats; and group 4 (fasted-LPS), 0.1 mg/kg LPS in fasted rats. Isolated liver perfusion, determination of liver PEPCK activity and liver PEPCK mRNA abundance, and a glucose tolerance test were performed at 4 hours in fed rats and at 6 hours in fasted rats. LPS induced hypoglycemia (1.62 +/- 0.33 mmol/L, P < .05) at 6 hours in group 2 (fed-LPS), but not in group 4 (fasted-LPS). Hyperinsulinemia was not observed in either group 2 (fed-LPS) or group 4 (fasted-LPS). In group 2 (fed-LPS), liver gluconeogenesis decreased (3.0 +/- 0.3 mg/g liver, P < .01). PEPCK activity decreased from 0.65 +/- 0.07 (group 1) to 0.23 +/- 0.02 U (P < .01). PEPCK mRNA abundance also decreased from 100% +/- 10% to 40% +/- 10%. The glucose disappearance rate (t1/2) increased (P < .05) in group 2 (fed-LPS) and group 4 (fasted-LPS).(ABSTRACT TRUNCATED AT 250 WORDS)