Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2

Islet amyloid polypeptide (LAPP), 'amylin', is the component peptide of islet amyloid formed in Type 2 diabetes. IAPP is expressed in islet beta-cells and is derived from a larger a precursor, proIAPP, by proteolysis. An in vitro translation/translocation system was used to separately examine processing of human proLAPP by the beta-cell endopeptidases PC2, PC3 or furin. ProIAPP was converted to mature IAPP by PC2 but there was little conversion by furin or PC3, These data are consistent with processing of proIAPP in beta-cell secretory granules, Abnormal cellular proteolysis associated with type 2 diabetes could contribute to LAPP amyloidosis.