Characterization of insulin, glucagon, and somatostatin from the river lamprey, Lampetra fluviatilis.

Insulin has been isolated from an extract of the pancreas of an Agnathan, the river lamprey Lampetra fluviatilis. The primary structure of the peptide (A-chain: GIVEQ CCHRK CSIYD MENYC N; B-chain: SALTG AGGTH LCGSH LVEAL YVVCG DRGFF YTPSK T) is the same as that of insulin from the sea lamprey Petromyzon marinus. In contrast, Lampetra glucagon (HAQGS FTSDY SKYLD SKQAK DFVIW LMNT), isolated from an extract of intestine, is structurally more similar to human glucagon (five amino acid substitutions) than to Petromyzon glucagon (six substitutions). Similarly, the primary structure of somatostatin (AAAAP GAAGG AQLPL GNRER KAGCK NFFWK TFSSC), isolated from Lampetra pancreas, contains eight amino acid substitutions and an additional residue compared with Petromyzon somatostatin. Somatostatin, isolated from Lampetra brain, has an identical structure to mammalian somatostatin-14 (AGCKN FFWKT FTSC), indicative of the same tissue-specific expression of different somatostatin genes that was previously observed in Petromyzon. In contrast to the reduced binding affinity of other fish insulins, lamprey insulin was equipotent with porcine insulin in inhibiting the binding of [3-[125I]iodotyrosine-A14] human insulin to the human insulin receptor.