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Small Clusters of Islet Amyloid Polypeptides May Contribute to Diabetes

Jan. 27, 2010 — A group led by Dr. Peter C. Butler of the University of California, Los Angeles, CA has discovered that small clusters (oligomers) of islet amyloid polypeptides (IAPPs) may contribute to the onset of type 2 diabetes mellitus.


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These results are presented in the February 2010 issue of The American Journal of Pathology.

Type 2 diabetes, or non-insulin-dependent diabetes, is characterized by high blood glucose in the presence of insulin resistance. Rates of diabetes doubled in the United States between 1990 and 2005, with nearly 23.6 million people diagnosed with diabetes.

In patients with type 2 diabetes, beta cells, the cells in the pancreas that secrete insulin, are progressively lost, and this loss is often associated with the accumulation of misfolded proteins, in particular IAPP. Similar amyloid protein accumulation has been implicated in the pathogenesis of diverse neurodegenerative diseases including Alzheimer, Parkinson's, and Huntington's disease. Gurlo et al explored the role of IAPP amyloids in type 2 diabetes pathology. They discovered that small clusters (oligomers) of IAPP formed within the beta cells and disrupted the membranes required for insulin secretion. These oligomers were also found in beta cells in human patients with type 2 diabetes. Moreover, IAPP oligomers also disrupted mitochondrial membranes, which can result in beta cell death.

Gurlo et al suggest that "IAPP toxic oligomers form within the secretory pathway in beta cells, to an increased extent in [type 2 diabetes] and as a function of obesity. … Taking the present study along with the known properties of toxic IAPP oligomers to induce membrane damage, we conclude that toxic oligomers may contribute to the beta cell dysfunction and apoptosis characteristic of type 2 diabetes."

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The above story is reprinted from materials provided by American Journal of Pathology, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Gurlo T, Ryazantsev S, Huang C-j, Yeh MW, Reber HA, Hines OJ, O'Brien TD, Glabe TG, Butler PC. Evidence for Proteotoxicity in beta-cells in Type 2 Diabetes, Toxic Islet Amyloid Polypeptide Oligomers form Intracellularly in the Secretory Pathway. American Journal of Pathology, 2010; 176: 861-869 DOI: 10.2353/ajpath.2010.090532
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