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 figure is presented}. 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 {A figure is presented}. 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.