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 (HSQGTFTSDY¹⁰ SKYLDNRRAQ²⁰DFIQWLMST), glucagon-like peptide-1 (GLP-1) (HADGTLTSDI¹⁰SSFLEKQATK²⁰ EFIAWLVSGR³⁰GRRQ), and glucagon-like peptide- 2 (GLP-2) (HADGSFTSDI¹⁰NKVLDTIAAK²⁰ EFLNWLISTK³⁰VTE). 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 anti its primary structure (APKEPEHPG¹⁰DASPEQLEKY²⁰ YQDLFQYIIF³⁰[TRPRY.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.