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

Abstract

To examine whether islet amyloid polypeptide (IAPP), other than through amyloid formation, may be of importance in diabetes pathogenesis, IAPP-deficient mice (IAPP− / −) were challenged with alloxan ( day 0). Diabetes in IAPP− / − mice was more severe at day 35, indicated by greater weight loss; glucose levels were higher in alloxan-treated IAPP− / − mice, whereas insulin levels were lower, indicating a greater impairment of islet function. Accordingly, glucose levels upon intravenous glucose challenges at days 7 and 35 were consistently higher in alloxan-treated IAPP− / −mice. At day 35, insulin mRNA expression, but not β-cell mass, was lower in untreated IAPP− / − mice. Yet, upon alloxan administration, β-cell mass and numbers of β-cell-containing islets were significantly more reduced in IAPP− / − mice. Furthermore, they displayed exaggerated β-cell dysfunction, because in their remaining β-cells, insulin mRNA expression was significantly more impaired and the localization of glucose transporter-2 was perturbed. Thus the lack of IAPP has allowed exaggerated β-cell cytotoxic actions of alloxan, suggesting that there may be beneficial features of IAPP actions in situations of β-cell damage.