title: Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure.
abstract: OBJECTIVE
  To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure (ALF).
  
  
  METHODS
  Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h. Plasma samples were withdrawn every five hours from a central vein. Three animals were used as controls and were maintained under anaesthesia only. Using (1)H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma samples.
  
  
  RESULTS
  No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia only. If we look at the ALF animals, we observed a statistically significant rise of lactate (P < 0.003) and pyruvate (P < 0.018) at the end of the experiments. We also observed statistically significant rises in the concentrations of alanine (P < 0.002), glycine (P < 0.005), threonine (P < 0.048), tyrosine (P < 0.000), phenylalanine (P < 0.000) and isoleucine (P < 0.01). Valine levels decreased significantly (P < 0.05).
  
  
  CONCLUSIONS
  Our pig model of ALF is characterized by an altered gluconeogenetic capacity, an impaired tricarboxylic acid (TCA) cycle and a glycolytic state.
authors.affiliation: Liver Cell Biology Laboratory, Department of Hepatology, University of Edinburgh, Edinburgh, EH16 4SA, United Kingdom. kostasophia@yahoo.com
authors.forename: Konstantinos J
authors.initials: KJ
authors.lastname: Dabos
authors.forename: Henry R
authors.initials: HR
authors.lastname: Whalen
authors.forename: Philip N
authors.initials: PN
authors.lastname: Newsome
authors.forename: John A
authors.initials: JA
authors.lastname: Parkinson
authors.forename: Neil C
authors.initials: NC
authors.lastname: Henderson
authors.forename: Ian H
authors.initials: IH
authors.lastname: Sadler
authors.forename: Peter C
authors.initials: PC
authors.lastname: Hayes
authors.forename: John N
authors.initials: JN
authors.lastname: Plevris
mesh_terms: D000082:Acetaminophen; D000596:Amino Acids / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002952:Citric Acid Cycle; D004195:Disease Models, Animal; D005943:Gluconeogenesis; D006019:Glycolysis; D019344:Lactic Acid / Q000097:blood; D008099:Liver / Q000378:metabolism*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D019289:Pyruvic Acid / Q000097:blood; D013552:Swine; D013997:Time Factors
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D019344:Lactic Acid; D000082:Acetaminophen; D019289:Pyruvic Acid