Glucose kinetics and development of endotoxin tolerance during long-term continuous endotoxin infusion

Alterations in glucose metabolism are seen following the acute administration of lethal doses (LD) and nonlethal doses of endotoxin, but relatively little information is available concerning glucose kinetics during long-term continuous endotoxin infusion. A nonlethal dose of endotoxin was administered intravenously to catheterized rats for up to 54 hours via a subcutaneously implanted osmotic pump; time-matched control animals were saline-infused. Glucose kinetics were assessed in vivo after 6, 30, and 54 hours of endotoxin by the constant infusion of [6-3H, U-14C]-glucose. The endotoxemic animals were hemodynamically stable throughout the experimental protocol and exhibited a febrile response at six and 30 hours of endotoxin infusion. Elevations in glucose turnover (50% and 42%) and recycling (140% to 150%) were seen after six and 30 hours of endotoxin infusion, but had returned to control values by 54 hours. A major portion (53% to 62%) of the increased glucose turnover in endotoxemic rats was accounted for by the elevated rate of recycling. The increased turnover appeared to be almost entirely due to enhanced gluconeogenesis and is consistent with the 160% to 170% elevation in plasma glucagon and increased lactate availability. After 54 hours, the plasma concentrations of glucose and lactate, glucose kinetics, and body temperature were not different between endotoxemic and control animals. In separate groups of rats, a bolus injection of endotoxin (LD 100) was administered to determine the presence of endotoxin tolerance. Endotoxin-infused animals showed improved survival after 30 and 54 hours (LD 20 and LD 0).(ABSTRACT TRUNCATED AT 250 WORDS)