Effect of acute glucagon removal on metabolic response to infection in conscious dog.
This study examined the acute role of glucagon in sustaining the increased hepatic gluconeogenesis observed in the conscious infected dog. After a basal sampling period, arterial glucagon levels were selectively decreased for 180 min by a peripheral infusion of somatostatin and basal intraportal infusion of insulin (GGN deficient; n = 6). In a separate protocol (GGN replaced; n = 5) glucagon was also infused intraportally to maintain the glucagon level at that seen during sepsis. Tracer and arteriovenous difference techniques were used to assess hepatic glucose metabolism and gluconeogenesis. In the GGN-deficient group the arterial plasma glucagon level fell from 416 +/- 49 to 88 +/- 21 pg/ml, whereas in the GGN-replaced group it remained elevated throughout (321 +/- 48 to 248 +/- 22 pg/ml). When glucagon was reduced, endogenous glucose production decreased by 1.6 +/- 0.3 mg.kg-1.min-1, and an exogenous glucose infusion was required to maintain euglycemia. Glucose metabolism remained unaltered when glucagon was replaced. When glucagon was deleted, net hepatic gluconeogenic precursor uptake was not altered. In contrast, the efficiency of gluconeogenesis was decreased by 33% compared with the GGN-replaced group. Liver biopsies taken at the end of the experiment indicated that a diversion of gluconeogenic carbon to glycogen accounted for 50% of the fall in gluconeogenic efficiency. In summary, the basal hyperglucagonemia seen during an infection helps sustain glucose production both through its effects on hepatic glycogen metabolism and on gluconeogenic efficiency.
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee 37232-0615.
O P
OP
McGuinness
D B
DB
Lacy
J
J
Anderson
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004285:Dogs; D004927:Escherichia coli Infections / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000502:physiology*; D005943:Gluconeogenesis; D006003:Glycogen / Q000378:metabolism; D006728:Hormones / Q000097:blood; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008297:Male
D001786:Blood Glucose; D006728:Hormones; D006003:Glycogen; D005934:Glucagon