Islet amyloid polypeptide (amylin)-deficient mice develop a more severe form of alloxan-induced diabetes

To examine whether islet amyloid polypeptide (IAPP), other than through amy loid formation, may be of importance in diabetes pathogenesis, IAPP-deficie nt mice (IAPP-(/)-) were challenged with alloxan (day 0). Diabetes in IAPP- (/)- mice was more severe at day 35, indicated by greater weight loss; gluc ose levels were higher in alloxan-treated IAPP-(/)- mice, whereas insulin l evels were lower, indicating a greater impairment of islet function. Accord ingly, glucose levels upon intravenous glucose challenges at days 7 and 35 were consistently higher in alloxan-treated IAPP-(/)- mice. At day 35, insu lin mRNA expression, but not beta-cell mass, was lower in untreated IAPP-(/ )- mice. Yet, upon alloxan administration, beta-cell mass and numbers of be ta-cell-containing islets were significantly more reduced in IAPP-/- mice. Furthermore, they displayed exaggerated beta-cell dysfunction, because in t heir remaining beta-cells, insulin mRNA expression was significantly more i mpaired and the localization of glucose transporter-2 was perturbed. Thus t he lack of IAPP has allowed exaggerated beta-cell cytotoxic actions of allo xan, suggesting that there may be beneficial features of IAPP actions in si tuations of beta-cell damage.