Structure and biological activity of glucagon and glucagon-like peptide from a primitive bony fish, the bowfin (Amia calva).
The bowfin, Amia calva (order Amiiformes) occupies an important position in phylogeny as a surviving representative of a group of primitive ray-finned fishes from which the present-day teleosts may have evolved. Glucagon and glucagon-like peptide (GLP) were isolated from an extract of bowfin pancreas and their primary structures determined. Bowfin glucagon shows only four amino acid substitutions compared with human glucagon, and bowfin glucagon was equipotent and equally effective as human glucagon in stimulation of glycogenolysis in dispersed hepatocytes from a teleost fish, the copper rockfish, Sebastes caurinus. In contrast, bowfin GLP shows 15 amino acid substitutions and three amino acid deletions compared with the corresponding region of human GLP-1-(7-37)-peptide. In particular, the bowfin peptide contains an N-terminal tyrosine residue rather than the N-terminal histidine residue found in all other glucagon-related peptides so far characterized. Bowfin GLP stimulated glycogenolysis in rockfish hepatocytes, but was 3-fold less effective and 23-fold less potent than human GLP-1-(7-37)-peptide. We speculate that selective mutations in the GLP domain of bowfin preproglucagon may be an adaptive response to the previously demonstrated low biological potency of bowfin insulin.
Conlon
J M
JM
Department of Biomedical Sciences, Creighton University Medical School, Omaha, NE 68178.
Youson
J H
JH
Mommsen
T P
TP
D000595:Amino Acid Sequence; D000818:Animals; D005399:Fishes; D005934:Glucagon / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D010179:Pancreas / Q000737:chemistry; D010446:Peptide Fragments; D010455:Peptides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid
D010446:Peptide Fragments; D010455:Peptides; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D006003:Glycogen; D005934:Glucagon; C051322:glucagon-like peptide 1 (7-37)