Hyperglucagonemia and hepatic glucose metabolism during infection in the conscious dog.
The chronic and acute roles of hyperglucagonemia in sustaining the increased glucose production observed in the conscious infected dog were examined. Three groups of dogs 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 min in INFXN by use of 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. Whereas the rate of glucose appearance (Ra) was increased by 30% (3.3 +/- 0.1 vs. 2.5 +/- 0.1 mg.kg-1.min-1) in INFXN vs. SHAM, Ra did not increase in SimGGN (2.4 +/- 0.2 mg.kg-1.min-1). 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-1.min-1, respectively. Net hepatic alanine fractional extraction in INFXN, leading to a greater rise in arterial blood alanine levels. In summary, chronic hyperglucagonemia alone cannot 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.
McGuinness
O P
OP
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Lacy
D B
DB
Eliasson
K
K
D000409:Alanine / Q000378:metabolism; D000818:Animals; D004285:Dogs; D004927:Escherichia coli Infections / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000097:blood* / Q000494:pharmacology; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D006728:Hormones / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male
D006728:Hormones; D005934:Glucagon; D005947:Glucose; D000409:Alanine