[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.
Yagui
K
K
Second Department of Internal Medicine, Chiba University School of Medicine.
Kanatsuka
A
A
Makino
H
H
D000682:Amyloid / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D004247:DNA; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D004247:DNA