Abstract

The expression of the preproglucagon gene in vertebrates is markedly species- and tissue-dependent. Three peptides derived from the posttranslational processing of preproglucagon were isolated from an extract of the pancreas of the urodeleAmphiuma tridactylum(three-toed amphiuma). The primary structures of the peptides indicated identity with glucagon (HSQGTFTSDY10SKYLDNRRAQ20DFIQWLMST), glucagon-like peptide-1 (GLP-1) (HADGTLTSDI10SSFLEKQATK20EFIAWLVSGR30GRRQ), and glucagon-like peptide-2 (GLP-2) (HADGSFTSDI10NKVLDTIAAK20EFLNWLISTK30VTE). Thus, in a urodele, as in the bullfrog but in contrast to the chicken and all nontetrapod species yet studied, pancreatic preproglucagon mRNA encodes a GLP-2 sequence. The amino acid sequence of glucagon has been better conserved during evolution of tetrapods (3 substitutions between amphiuma and human) than the sequences of either GLP-1 (7 substitutions) or GLP-2 (15 substitutions). Pancreatic polypeptide was also isolated from the extract and its primary structure (APKEPEHPGD10DASPEQLEKY20YQDLFQYIIF30ITRPRY.NH2) indicates that the amino acid sequence of this peptide has been very poorly conserved, even among the amphibia. Amphiuma pancreatic somatostatin is identical to mammalian somatostatin-14.

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