title: Metabolic and endocrine functions of glucagon-like peptides - evolutionary and biochemical perspectives.
abstract: In amphibians and mammals, the preproglucagon gene encodes two related GLPs - GLP-1(37 residues) and GLP-2 (34 residues). The physiologically functional GLPs, however, are GLP-17-36amide, or similar, truncated forms of GLP-1. While the liver is devoid of GLP receptors and fails to respond metabolically, brain, gastric cells and pancreatic cells have been identified as potential target sites. These tissues possess specific binding sites for truncated GLP-1, and generally, cells respond to truncated GLPs with increases in CAMP. In mammalian pancreas, truncated GLPs function as powerful insulinotropins, while also increasing insulin gene transcription and inhibiting glucagon release. Full length GLP-1 is a weak insulinotropin only. To date, neither metabolic nor endocrine actions have been assigned to GLP-2.Following processing of preproglucagon gene products, fish pancreas and intestine contain only one GLP (31 residues) displaying considerable sequence homology with GLP-17-36. Applied in low nanomolar concentrations, fish GLPs, together with GLP-17-36, activate hepatic glycogenolysis, gluconeogenesis and lipolysis in fishes. Thousand-fold higher levels of GLP-17-37 are required to elicit comparable metabolic effects. Generally, the metabolic actions of GLPs are similar to those for glucagon, but GLPs tend to be more potent in their specific actions. Fish livers possibly contain GLP receptors distinct from glucagon receptors. Message transduction in some, but not all fish species, may involve adenylyl cyclase and CAMP, but correlation between metabolic activation and cAMP levels is generally poor. Fish GLP seems to be a very weak insulinotropin in Brockmann bodies.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, WA, Canada.
authors.forename: T P
authors.initials: TP
authors.lastname: Mommsen
authors.forename: E M
authors.initials: EM
authors.lastname: Plisetskaya