Insulin and proglucagon-derived peptides from the horned frog, Ceratophrysornata (Anura : Leptodactylidae)

Insulin and peptides derived from the processing of proglucagon have been i solated from an extract of the pancreas of the South American horned frog, Ceratophrys ornata (Leptodactylidae). Ceratophrys insulin is identical to t he insulin previously isolated from the toad, Bufo marinus (Bufonidae). Cer atophrys glucagon was isolated in two molecular forms with 29- and 36-amino acid residues in approximately equal amounts. Glucagon-29 is identical to glucagon from B. marinus and from the bullfrog, Rana catesbeiana (Ranidae) and contains only 1 amino acid substitution (Thr(29) --> Ser) compared with glucagon from Xenopus laevis (Pipidae). Glucagon-36 comprises glucagon-29 extended from its C-terminus by Lys-Arg-Ser-Gly-Gly-Met-Ser. This extension is structurally dissimilar to the C-terminal octapeptide of mammalian oxyn tomodulin and resembles more closely that found in C-terminally extended gl ucagons isolated from fish pancreata. Ceratophrys glucagon-like peptide-1 ( GLP-1) (His-Ala-Asp-Gly-Thr-Tyr-Gln-Asn-Asp-Val(10)-Gln-Gln-Phe-Leu-Glu-Glu -Lys-Ala-Ala-Lys(20)-Glu-Phe-Ile-Asp-Trp-Leu-Ile-Lys-Gly- Lys(30)-Pro-Lys-L ys-Gln-Arg-Leu-Ser) contains 3 amino acid substitutions compared with the c orresponding peptide from B. marinus, 8 substitutions compared with GLP-1 f rom R. catesbeiana, and between 4 and 11 substitutions compared with the th ree GLP-1 peptides identified in X. laevis proglucagon. GLP-2 was not ident ified in the extract of Ceratophrys pancreas. The data indicate that, despi te its importance in the regulation of glucose metabolism, the primary stru cture of GLP-1 has been very poorly conserved during evolution, even among a single order such as the Anura. (C) 1999 Academic Press.