Characterization of insulins and proglucagon-derived peptides from a phylogenetically ancient fish, the paddlefish (Polyodon spathula).
The North American paddlefish, Polyodon spathula (Order Acipenseriformes) is an extant representative of a group of primitive Actinopterygian (ray-finned) fish that probably shared a common ancestor with present-day teleosts. Two molecular forms of insulin which differ by a single amino acid substitution, His or Asp at position 15 of the A chain, were isolated from the pancreas of the paddlefish. Paddlefish insulins show greatest structural similarity to insulin from the garfish (order Lepisosteiformes) and resemble mammalian insulins more strongly than do insulins from teleost fish. The primary structures of several proglucagon-derived peptides, two molecular forms of glucagon which differ by the single amino acid substitution Arg18-->Ser, and glucagon-like peptide, have been less well conserved during evolution. The paddlefish glucagons contain 31 amino acid residues, rather than the usual 29, and show several structural features, such as Met5, Glu24 and Gly29, not previously observed in glucagons from other species. In spite of considerable differences in structure between paddlefish and mammalian glucagons (10 or 11 amino acid substitutions), both paddlefish glucagons are equally as effective as bovine glucagon in stimulating glycogenolysis in dispersed hepatocytes from the teleost fish Sebastes caurinus (rockfish). However, the substitution Arg18-->Ser in the paddlefish glucagon results in a 6-fold decrease in potency in this system.
Nguyen
T M
TM
Regulatory Peptide Center, Creighton University School of Medicine, Omaha, NE 68178.
Mommsen
T P
TP
Mims
S M
SM
Conlon
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005399:Fishes / Q000145:classification / Q000235:genetics*; D005934:Glucagon / Q000737:chemistry*; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000302:isolation & purification*; D008112:Liver Glycogen / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism; D010802:Phylogeny; D052336:Proglucagon; D011498:Protein Precursors / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D007328:Insulin; D008112:Liver Glycogen; D010455:Peptides; D011498:Protein Precursors; D052336:Proglucagon; D005934:Glucagon