[Construction of transgenic mouse system expressing human islet amyloid polypeptide (IAPP)/amylin]

To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we generated transgenic mice using a human IAPP cDNA connected to an insulin promoter. Analyses by RNA blotting and immunohistochemistry revealed that the transgene was expressed exclusively in the pancreatic Beta-cells. Immunogold electron microscopy showed that the C-terminal flanking peptide of the human IAPP was localized in the Beta-secretory granules. Reverse-phase HPLC demonstrated the presence of mature human IAPP. However, glucose tolerance was normal and amyloid formation was not observed in transgenic mice at 7 months of age. A longer time or other factors may be required for islet amyloid deposits and hyperglycemia to develop in mice.