Hyperglucagonemia and hepatic glucose metabolism during infection
in the conscious dog.
Mguinness, Owen P., D. Brooks Lacy, Katherine Eliasson.
Department of Molecular Physiology and Biophysics, Vanderbilt
University School of Medicine, Nashville, TN 37232-0615
APStracts 2:0240E, 1995.
The chronic and acute role of hyperglucagonemia in sustaining the
increased glucose production observed in the conscious infected dog
was examined. Three groups were studied: a sham group(SHAM; n=10), an
infected group (INFXN; n=11) and a sham group in which the chronic
(42 h) increase in glucagon observed in INFXN was simulated (SimGGN;
n=5). INFXN and SimGGN were studied in the presence of
hyperglucagonemia. In addition glucagon was selectively decreased for
180 minutes in INFXN using somatostatin with basal intraportal
insulin replacement and in SimGGN by discontinuing the exogenous
glucagon infusion. Tracer and arteriovenous difference techniques
were used to assess hepatic glucose metabolism and gluconeogenesis.
While the rate of glucose appearance (Ra) was increased by 30%
(3.3+/-0.1 vs 2.5+/-0.1 mg/kg/min) in INFXN vs SHAM, Ra did not
increase in SimGGN (2.4+/-0.2 mg/kg/min). In addition, the 30%
increase in net hepatic gluconeogenic precursor uptake seen in INFXN
did not occur in SimGGN, despite an augmented net hepatic alanine
fractional extraction (0.62+/-0.03 vs 0.47+/-0.05; SimGGN vs INFXN).
With acute removal of hyperglucagonemia endogenous Ra decreased in
SimGGN and INFXN by 1.0+/-0.2 and 1.4+/-0.3 mg/kg/min, respectively.
Net hepatic alanine fractional extraction decreased in both groups,
however it fell more rapidly in INFXN leading to a greater rise in
arterial blood alanine levels. In summary, chronic hyperglucagonemia
alone can not explain the increase in Ra observed during an
infection. The marked hyperglucagonemia seen during infection plays
an essential role in sustaining normal net hepatic fractional alanine
extraction to compensate for an impairment in glucagon stimulated
hepatic amino acid transport activation .
Received 5 June 1995; accepted in final form 18 July 1995.
APS Manuscript Number E257-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95