Hepatic glycogen accurately reflected by acetaminophen glucuronide
in dogs refed after fasting.
Rother, Kristina I., W. Frederick Schwenk.
Department of Pediatrics, Mayo Clinic, Rochester, Minnesota
55905
APStracts 2:0108E, 1995.
To validate a method to "biochemically biopsy" the immediate
precursor of intrahepatic glycogen [uridyl-diphosphate (UDP)-glucose]
using acetaminophen and to assess how fasting affects the direct and
indirect pathways of glycogen synthesis, dogs were fasted overnight
(group 1, N=5) or for 2.5 days (group 2, N=5), and then received a 4
-h duodenal infusion of unlabeled glucose, [3-3H]glucose and [U
-14C]lactate to label hepatic glycogen via the direct and indirect
pathways, respectively, and [1-13C]galactose to measure intrahepatic
UDP-glucose flux. After 3 hours for equilibration, acetaminophen was
given and urine collected for acetaminophen glucuronide. Multiple
liver biopsies were obtained. The mean 3H/14C ratios of glucose
derived from glycogen [10.4+/-4.1 (group 1), 1.1+/-0.3 (group 2)] and
glucose derived from acetaminophen glucuronide (11.5+/-4.0, 1.0+/
-0.1, respectively) were similar. Fasting significantly increased UDP
-glucose flux, the rate of glycogen synthesis, and the contribution of
the indirect pathway. We conclude that in dogs, 1) no functional
hepatic zonation exits with regard to acetaminophen glucuronidation
and liver glycogen synthesis; and 2) with appropriate choice of
isotopic tracers and study design, UDP-glucose flux can accurately
reflect rates of hepatic glycogen synthesis.
Received 19 October 1994; accepted in final form 10 May 1995.
APS Manuscript Number E431-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.