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 polypeptide (IAPP) have been created to study development of islet amyloid and its impact on islet cell function. The tendency to form islet amyloid has varied strongly among these strains by factors that have not been elucidated. Because some beta cell granule components are known to inhibit IAPP fibril formation in vitro, we wanted to determine whether a mouse strain expressing human IAPP but lacking the nonamyloidogenic mouse IAPP is more prone to develop islet amyloidosis.


METHODS
Such a strain was created by cross-breeding a transgenic 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 expressing both human and mouse IAPP. Supporting these results, we found that mouse IAPP dose-dependently inhibits formation of fibrils from human IAPP.


CONCLUSIONS
Female mice did not develop amyloid deposits, although small extracellular amorphous IAPP deposits were found in some islets. When cultivated in vitro, amyloid deposits occurred within 10 days in islets from either male or female mice expressing only human IAPP. The study shows that formation of islet amyloid may be dependent on the environment, including the presence or absence of fibril inhibitors or promoters.
Westermark
G T
GT
Department of Biomedicine and Surgery, Linköping University, Sweden. gunwe@IBK.liu.se
Gebre-Medhin
S
S
Steiner
D F
DF
Westermark
P
P
D000682:Amyloid / Q000096:biosynthesis* / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics; D000818:Animals; D001835:Body Weight; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004777:Environment; D005260:Female; D006720:Homozygote; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000473:pathology; D012737:Sex Factors; D013997:Time Factors
D000682:Amyloid; D004041:Dietary Fats; D058228:Islet Amyloid Polypeptide