Isolation and structural characterization of proglucagon-derived peptides, pancreatic polypeptide, and somatostatin from the urodele Amphiuma tridactylum

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 urodele Amphiuma tridactylum (three-toed amphiuma). The primary structures of the peptides indicated identity with glucagon (HSQGTFTSDY(10)SKYLDNRRAQ(20)DFIQWLMST), glucagon-like peptide-1 (GLP-1) (HADGTLTSDI(10)SSFLEKQATK(20)EFIAWLVSGR(30)GRRQ), and glucagon-like peptide-2 (GLP2) (HADGSFTSDI(10)NKVLDTIAAK(20)EFLNWLISTK(30)VTE). Thus, in a urodele, as in the bullfrog but in contrast to the chicken and all non tetrapod 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 (APKEPEHPGD(10)DASPEQLEKY(20)YQDLFQYIIF(30)ITRPRY.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.