Islet amyloid development in a mouse strain lacking endogenous islet amyloid polypeptide (IAPP) but expressing human IAPP

Background: Several mouse strains expressing human islet amyloid polypeptid e (IAPP) have been created to study development of islet amyloid and its im pact on islet cell function. The tendency to form islet amyloid has varied strongly among these strains by factors that have not been elucidated. Beca use some beta cell granule components are known to inhibit IAPP fibril form ation in vitro, we wanted to determine whether a mouse strain expressing hu man IAPP but lacking the nonamyloidogenic mouse IAPP is more prone to devel op islet amyloidosis. Materials and Methods: Such a strain was created by cross-breeding a transg enic mouse strain and an IAPP null mouse strain. Results: when fed a fat-enriched diet, male mice expressing only human IAPP developed islet amyloid earlier and to a higher extent than did mice expre ssing both human and mouse IAPP. Supporting these results, we found that mo use IAPP dose-dependently inhibits formation of fibrils from human IAPP. Conclusions: Female mice did not develop amyloid deposits, although small e xtracellular amorphous IAPP deposits were found in some islets. When cultiv ated in vitro, amyloid deposits occurred within 10 days in islets from eith er male or female mice expressing only human IAPP. The study shows that for mation of islet amyloid may be dependent on the environment, including the presence or absence of fibril inhibitors or promoters.