Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide.
Open accessAbstract
Pancreatic islet amyloid deposits are a characteristic pathologic feature of non-insulin-dependent diabetes mellitus and contain islet amyloid polypeptide (IAPP; amylin). We used transgenic mice that express human IAPP in pancreatic beta cells to explore the potential role of islet amyloid in the pathogenesis of non-insulin-dependent diabetes mellitus. Extensive amyloid deposits were observed in the pancreatic islets of approximately 80% of male transgenic mice > 13 months of age. Islet amyloid deposits were rarely observed in female transgenic mice (11%) and were never seen in nontransgenic animals. Ultrastructural analysis revealed that these deposits were composed of human IAPP-immunoreactive fibrils that accumulated between beta cells and islet capillaries. Strikingly, approximately half of the mice with islet amyloid deposits were hyperglycemic (plasma glucose > 11 mM). In younger (6- to 9-month-old) male transgenic mice, islet amyloid deposits were less commonly observed but were always associated with severe hyperglycemia (plasma glucose > 22 mM). These data indicate that expression of human IAPP in beta cells predisposes male mice to the development of islet amyloid and hyperglycemia. The frequent concordance of islet amyloid with hyperglycemia in these mice suggests an interdependence of these two conditions and supports the hypothesis that islet amyloid may play a role in the development of hyperglycemia.
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- Authors
- Verchere, C. B., D'Alessio, D. A., Palmiter, R. D., Weir, G. C., Bonner-Weir, S., Baskin, D. G., & Kahn, S. E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, Howard Hughes Medical Institute, University of Washington, Seattle 98195, USA.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-04-16
- Volume
- 93
- Issue
- 8
- Pages
- 3492-3496
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC39637
- OpenAlex
- W2126264030
- Cited by
- 278
- References
- 31
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 4 · 2018: 9 · 2017: 7 · 2016: 9 · 2015: 7 · 2014: 10 · 2013: 7 · 2012: 15
- FWCI
- 10.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Washington (DK17047, DK-35816)
- Medical Research Council Canada
- National Institutes of Health (2r01dk012829-36, DK 36836)
- Medical Research Council
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-35816, DK 12829, DK-17047, P30DK035816, P30DK017047)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- islet amyloid, amylin, hyperglycemia, type 2 diabetes, pancreatic beta cells, transgenic mice, amyloid deposits, sex differences, islet ultrastructure, fibril formation
- MeSH terms
- Amyloid, Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Female, Humans, Hyperglycemia, Insulin, Islets of Langerhans, Male, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Recombinant Proteins, Gene Expression, Microscopy, Immunoelectron, Mice, Islet Amyloid Polypeptide
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