ALTERATIONS IN HEPATIC GLUCONEOGENIC AMINO-ACID-UPTAKE AND GLUCONEOGENESIS IN THE ENDOTOXIN-TREATED CONSCIOUS DOG

We examined the effect of a 240 min intraportal infusion of a nonletha l dose of Escherichia coli endotoxin (.21 mu g.kg(-1).min(-1)) on hepa tic amino acid and glucose metabolism in chronically catheterized 42 h fasted conscious dogs (n = 8). Hepatic metabolism was assessed using tracer (3-[H-3]glucose [U-C-14]alanine) and arteriovenous difference t echniques. After endotoxin administration net hepatic glucose output i ncreased twofold. Arterial plasma insulin levels decreased by 25%, whe reas arterial plasma glucagon and cortisol levels increased 10- and 6- fold, respectively. Arterial lactate levels increased 6.4-fold, wherea s net hepatic lactate uptake was not increased. Arterial alanine level s (1.6-fold) and net hepatic alanine uptake (1.3-fold) increased, wher eas net hepatic alanine fractional extraction was unaltered. In contra st, the arterial levels of the other gluconeogenic amino acids (glutam ine, glycine, serine, and threonine) decreased. Despite this decrease, net uptake of these amino acids by the liver did not decrease, becaus e net hepatic amino acid fractional extraction increased. Total net he patic gluconeogenic precursor uptake was unaltered (1.1 +/- .1 to 1.3 + .3 mg.kg(-1).min(-1) expressed in glucose equivalents). In summary, gluconeogenesis does not increase after endotoxin administration. Thus , an increase in net hepatic glycogenolysis accounts for the majority of the increase in hepatic glucose production. The lack of an increase in alanine fractional extraction, despite hyperglucagonemia and a ris e in the fractional extraction of other gluconeogenic amino acids, sug gests that endotoxin specifically impairs hepatic alanine entry in viv o.