AJP - Regulatory, Integrative and Comparative Physiology, Vol 244, Issue 6 794-R800, Copyright © 1983 by American Physiological Society
Regulation of glucose production from lactate in experimental sepsis
M. G. Clemens, I. H. Chaudry, P. H. McDermott and A. E. Baue
Gluconeogenic and oxidative capabilities with lactate as a substrate were
studied in perfused livers isolated from rats in late sepsis. Glucose
release in the presence of 5 mM lactate was significantly depressed in
livers from septic rats. When gluconeogenesis was stimulated by
phenylephrine, livers from septic rats exhibited both a decreased
sensitivity and lower maximal rate of glucose release when compared with
livers from sham-operated rats. Oxygen consumption (VO2) by perfused livers
from septic rats was also depressed under the above conditions. The
addition of lysine in concentrations greater than 0.5 mM restored glucose
production in livers from septic rats to a rate not different from
sham-operated controls but did not restore VO2. However, inclusion of
lysine (5 mM) in the perfusate was not able to restore sensitivity to
stimulation by phenylephrine in livers from septic rats. Although hepatic
ATP levels were depressed in sepsis, the decrease was not sufficient to
explain the decreased rates of glucose production. We conclude from these
results that primary cellular defects in gluconeogenic and oxidative
capabilities occur during sepsis that are independent of inadequate
perfusion.
