The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide.
Open accessAbstract
The islet in non-insulin-dependent diabetes mellitus (NIDDM) is characterized by loss of beta cells and large local deposits of amyloid derived from the 37-amino acid protein, islet amyloid polypeptide (IAPP). We have hypothesized that IAPP amyloid forms intracellularly causing beta-cell destruction under conditions of high rates of expression. To test this we developed a homozygous transgenic mouse model with high rates of expression of human IAPP. Male transgenic mice spontaneously developed diabetes mellitus by 8 weeks of age, which was associated with selective beta-cell death and impaired insulin secretion. Small intra- and extracellular amorphous IAPP aggregates were present in islets of transgenic mice during the development of diabetes mellitus. However, IAPP derived amyloid deposits were found in only a minority of islets at approximately 20 weeks of age, notably after development of diabetes mellitus in male transgenic mice. Approximately 20% of female transgenic mice spontaneously developed diabetes mellitus at 30+ weeks of age, when beta-cell degeneration and both amorphous and amyloid deposits of IAPP were present. We conclude that overexpression of human IAPP causes beta-cell death, impaired insulin secretion, and diabetes mellitus. Large deposits of IAPP derived amyloid do not appear to be important in this cytotoxicity, but early, small amorphous intra- and extracellular aggregates of human IAPP were consistently present at the time of beta-cell death and therefore may be the most cytotoxic form of IAPP.
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Cites
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Self-citationIslet Amyloid, Islet-Amyloid Polypeptide, and Diabetes Mellitus
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Inflammasomes: mechanism of action, role in disease, and therapeutics
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Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
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Metadata
- Authors
- Janson, J., Soeller, W. C., Roche, P. C., Nelson, R. T., Torchia, A. J., Kreutter, D. K., & Butler, P. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1996-07-09
- Volume
- 93
- Issue
- 14
- Pages
- 7283-7288
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1976597734
- Cited by
- 342
- References
- 20
- FWCI
- 8.75
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Janson, J., Soeller, W. C., Roche, P. C., Nelson, R. T., Torchia, A. J., Kreutter, D. K., & Butler, P. C. (1996). Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.93.14.7283
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