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Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus

Nature volume 368, pages 756–760 (1994)Cite this article

Abstract

THE 37-amino-acid polypeptide amylin is the principal constituent of the amyloid deposits that form in the islets of Langerhans in patients with type-2 diabetes mellitus1–5, but its role in the pathogenesis of this disease is unresolved6–8. In view of the fact that the β-amyloid protein that forms fibrils in Alzheimer's disease is toxic to neurons 9,10, we have investigated whether amylin fibrils could be toxic to pancreatic islet cells. We show here that human amylin is toxic to insulin-producing β-cells of the adult pancreas of rats and humans. This toxicity is mediated by the fibrillar form of the amylin peptide and requires direct contact of the fibrils with the cell surface. The mechanism of cell death involves RNA and protein synthesis and is characterized by plasma membrane blebbing, chromatin condensation and DNA fragmentation, indicating that amylin induces islet cell apoptosis. These findings indicate that amylin fibril formation in the pancreas may cause islet cell dysfunction and death in type-2 diabetes mellitus.

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Author notes

  1. Bruce A. Yankner: To whom correspondence should be addressed

Authors and Affiliations

  1. Department of Neurology, Harvard Medical School and The Children's Hospital, Enders 260, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Alfredo Lorenzo, Bronwyn Razzaboni & Bruce A. Yankner

  2. Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, 02215, USA

    Gordon C. Weir

Authors
  1. Alfredo Lorenzo
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  2. Bronwyn Razzaboni
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  3. Gordon C. Weir
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  4. Bruce A. Yankner
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Lorenzo, A., Razzaboni, B., Weir, G. et al. Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature 368, 756–760 (1994). https://doi.org/10.1038/368756a0

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