Isolation and sequence determination of two N-terminal fragments of islet amyloid polypeptide in rat pancreas.

Using a highly sensitive and specific radioimmunoassay (RIA) for the N-terminal hexadecapeptide of islet amyloid polypeptide (IAPP), we isolated two N-terminal fragments of IAPP from rat pancreas. They were identified as IAPP(1-16) and IAPP(1-17) by amino acid sequencing. The two fragments were also found in rat plasma. IAPP(1-37) was the major molecular form of rat IAPP, IAPP(1-16) and IAPP(1-17) accounting for 6.0% and 32.3% of the immunoreactivity for the N-terminal region of the peptide in pancreata of normally fed rats. In human pancreas, the N-terminal fragments of IAPP were not present, indicating that the processing of IAPP in the pancreas differs between human and rat. Food deprivation increased the molar ratios of IAPP(1-16) and IAPP(1-17) to IAPP(1-37) in comparison to values for fed rats. Identification of novel fragments of IAPP, in addition to IAPP(1-37), offers a promise for the elucidation of the physiological function of IAPP and the identification of factors that regulate the biosynthesis and catabolism of the peptide.