Metabolic actions of glucagon-family hormones in liver

This review addresses direct and indirect metabolic actions of hormones co-encoded in the preproglucagon gene of fishes. Emphasis is placed on a critical analysis of the effects of glucagon and glucagon-like peptide (GLP) and the current knowledge of the respective modes of action is reviewed. In mammals GLPs exert no direct metabolic actions. In fish liver, GLP and glucagon act on similar targets of intermediary metabolism by enhancing flux through glycogenolysis, lipolysis and gluconeogenesis. Increases in substrate oxidation are not uniform. Hormonal activation of glycogen phosphorylase and triglyceride lipase and inhibition of pyruvate kinase are implicated in these actions. Hormone-dependent hyperglycemia, depletion of hepatic glycogen and increases in free fatty acids are noticeablein vivo. Glucagon also activates hepatic amino acid uptake and ammonia excretion. Glucagon actions are accompanied by large increases in hepatic cAMP and increased phosphorylation of pyruvate kinase. Metabolic effects measured after GLP administration are associated with minor, if any, increases in cAMP and effects on pyruvate kinase are variable. We hypothesize that different hepatic receptors with differing modes of intracellular message transduction are involved in glucagon and GLP actions while targetting identical metabolic routes. Responses of different species of fish cover a wide spectrum, and variation of response with the circannual cycle of experimental animals makes comparisons of results, even within one species, difficult.