Gluconeogenesis and phosphoenergetics in rat liver during endotoxemia.

BACKGROUND

During endotoxemia, glucose and energy metabolism varies depending on the stage, severity, and other conditions. In this study, gluconeogenesis from 13C-labeled alanine and phosphoenergetic state in rat liver during the acute phase of endotoxemia were concurrently observed by in vivo 13C and 31P NMR spectroscopy in a noninvasive manner.

MATERIALS AND METHODS

Lipopolysaccharide from Escherichia coli (10 mg/kg) was injected intravenously followed by infusion of [3-13C]alanine. In vivo 13C and 31P NMR spectra were alternately collected for 90 min with a 2.0 Tesla CSI Omega System.

RESULTS

In our experimental model, endotoxin increased the pulse rate without decreasing the blood pressure and elevated the blood sugar level, which suggests the so-called hyperdynamic state. Even under such conditions, a slight, but significant, impairment of the phosphoenergetic state in the liver (a decrease in ATP and an increase in Pi) was detected with 31P NMR spectroscopy. The 13C peaks of glucose C6 and Glu/Gln C2 of the liver in endotoxemia were significantly lower than those of the control, despite hyperglycemia in endotoxemia.

CONCLUSIONS

NMR spectroscopic studies suggest that the endotoxin caused the inhibition of gluconeogenic activity from the infused [3-13C]alanine and the TCA cycle accompanied by a deterioration in the phosphoenergetic state even in the hyperglycemic phase. Since the blood sugar level might be influenced by the systemic utilization of glucose, such direct measurements should prove important in the in vivo evaluation of glucose and energy metabolism in the liver.