Multiple molecular forms of insulin and glucagon-like peptide from the Pacific ratfish (Hydrolagus colliei)

The primary structure of an insulin isolated from the pancreas of the holocephalan fish, Hydrolagus colliei (Pacific ratfish), has been established as A-chain: GIVEQCCHNTCSLANLEGYCN B-chain: VPTQRLCGSHLVDALYFVCGERGFFYSPKPIRELEPLL. Three further molecular forms of insulin were also isolated and shown to have the same A-chain but truncated B-chains of 31-, 36-, and 37-amino acid residues. It is proposed that all four insulins arise from a single proinsulin by proteolytic cleavages at different sites within the C-peptide region. The insulin with 38 amino acids in the B-chain was equipotent with human insulin in inhibiting the binding of radiolabelled human insulin to rat fat cells but the maximum effect of ratfish insulin upon the transport of 3-O-methylglucose into the cells was only 65% of the maximum effect of human insulin. Two molecular forms of glucagon-like peptide were isolated from the ratfish pancreas. The primary structure of the more abundant peptide was established as HADGIYTSDVASLTDYLKSKRFVESLSNYNRKQND. The primary structure of the second peptide was the same except that it was extended from the C-terminus by the sequence RRM. It is probable, therefore, that both glucagon-like peptides also arise from a single proglucagon by different pathways of post-translational processing.