PROCESSING OF PRO-ISLET AMYLOID POLYPEPTIDE (PROIAPP) BY THE PROHORMONE CONVERTASE PC2

Islet amyloid polypeptide (LAPP), 'amylin', is the component peptide o f islet amyloid formed in Type 2 diabetes. IAPP is expressed in islet beta-cells and is derived from a larger a precursor, proIAPP, by prote olysis. An in vitro translation/translocation system was used to separ ately examine processing of human proLAPP by the beta-cell endopeptida ses PC2, PC3 or furin. ProIAPP was converted to mature IAPP by PC2 but there was little conversion by furin or PC3, These data are consisten t with processing of proIAPP in beta-cell secretory granules, Abnormal cellular proteolysis associated with type 2 diabetes could contribute to LAPP amyloidosis.