Metabolic effects of glucagon in endotoxemic minipigs.
A treatment group of four 50-80-kg Yucatan minipigs was fitted with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate transhepatic kinetics of glucose, lactate, and insulin. Three days later, they were placed in slings, and a primed-continuous intravenous infusion of 3-tritiated glucose was initiated to monitor whole body glucose kinetics. Following a 3-hour control period, an intravenous infusion of E. coli endotoxin was administered at 15 micrograms/kg/hr for 6 hours. After 1 hour of endotoxin infusion, glucagon was administered as a primed (50 micrograms/kg)-continuous (50 micrograms/kg/hr) intravenous infusion for 5 hours. These results were compared statistically to a control group of eight minipigs given endotoxin only. Glucagon caused a transient (less than 1 hour) peak elevation of arterial glucose levels due to increased hepatic glycogenolysis immediately following initiation of the glucagon infusion. Despite enhanced extrahepatic (renal) gluconeogenesis, plasma glucose concentrations decreased to the hypoglycemic levels of the control group, as glucagon was unable to overcome the relative endotoxic inhibition of hepatic gluconeogenesis. Pancreatic output of insulin increased sixfold resulting in threefold increments in transhepatic uptake and arterial serum insulin levels. Arterial lactate and pyruvate concentrations were elevated due to increased peripheral production and hepatic output. Survivability in the treatment group (75%) improved over the control group (33%).
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004731:Endotoxins / Q000008:administration & dosage; D004926:Escherichia coli; D005934:Glucagon / Q000627:therapeutic use*; D005943:Gluconeogenesis; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism; D011773:Pyruvates / Q000097:blood; D019289:Pyruvic Acid; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014115:Toxemia / Q000188:drug therapy* / Q000378:metabolism
D001786:Blood Glucose; D004731:Endotoxins; D007328:Insulin; D007773:Lactates; D008112:Liver Glycogen; D011773:Pyruvates; D019344:Lactic Acid; D019289:Pyruvic Acid; D005934:Glucagon