The pancreatic peptide hormones insulin, glucagon, and glucagon-like peptide (GLP) modify metabolic flux in rainbow trout liver. This study quantifies the plasma titres of these peptide hormones using homologous radioimmunoassays after a 6-week fast and the coincident changes in specific enzymes in the liver. Fasting significantly changed a number of body parameters and depressed the plasma concentrations of each hormone, with the fall in insulin being the greatest and that in GLP the least. The relative hormone decline was such that the molar ratio of the glucagon-family peptides/insulin actually increased. Liver gluconeogenic enzymes were activated and pyruvate kinase underwent an apparent phosphorylation as indicated by altered kinetic parameters. These enzyme changes are evidence for an enhanced liver potential for gluconeogenesis during fasting. It is suggested that the changes in hormone molar ratios are responsible for the observed enzyme changes and are also key in the coordinated regulation of carbohydrate metabolism in the trout during fasting.
Plasma and liver composition, liver enzyme activities, and metabolite flux in isolated hepatocytes have been studied in immature American eels,Anguilla rostrata, injected daily IP with saline or cortisol (0.35 mg/kg eel). Plasma cortisol values were significantly increased above saline controls in those eels receiving cortisol at 3h and 6h following the final (tenth) injection. On day 6 and 10 of injection plasma cortisol levels were significantly below saline controls 24h following cortisol injection. Plasma glucose values were significantly depressed in the cortisol-injected eels at both 6 and 24h following the final (tenth) injection. At the 24h sampling time, plasma protein had significantly increased, but there was no change in either plasma amino acid or fatty acid levels. An increased hepatosomatic index was attributed to a major increase in total lipids, as both protein and glycogen contents were decreased. Of the liver enzymes assayed, significant activity changes occurred only for lactate dehydrogenase (decreased), mitochondrial citrate synthase (increased) and phosphoenolpyruvate carboxykinase (increased) 24h following the final (tenth) cortisol injection. Although enzyme activity changes implied increased liver gluconeogenesis, the absolute rate of lactate, alanine, and aspartate incorporation into glucose declined in viable hepatocytes isolated from cortisol-injected eels compared to the saline controls. Relative changes in metabolite flux did support a preferential increase in gluconeogenesis from amino acids. These results are consistent with the increase in amino acid gluconeogenesis as a result of cortisol administration implied in previous studies, but failed to show a definitive cortisol effect on this pathway in the eel liver. It is suggested that other hormones (e.g. thyroxine, catecholamines, glucagon) may interact in a complex way with cortisolin vivo to bring about the biochemical changes observed in this study. The rapid clearance of exogenously injected cortisol noted in this study makes causal relationships between the injected hormone and any observed metabolic effect in the intact animal difficult.
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