Islet Amyloid Polypeptide: Structure, Function, and PathophysiologyReport as inadecuate




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Journal of Diabetes Research - Volume 2016 2016, Article ID 2798269, 18 pages -

Review Article

Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA

Diabetes Research Program, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA

Research Department of Structural and Molecule Biology, University College London, Gower Street, London WC1E 6BT, UK

Received 27 February 2015; Accepted 24 April 2015

Academic Editor: Lucie Khemtemourian

Copyright © 2016 Rehana Akter et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The hormone islet amyloid polypeptide IAPP, or amylin plays a role in glucose homeostasis but aggregates to form islet amyloid in type-2 diabetes. Islet amyloid formation contributes to β-cell dysfunction and death in the disease and to the failure of islet transplants. Recent work suggests a role for IAPP aggregation in cardiovascular complications of type-2 diabetes and hints at a possible role in type-1 diabetes. The mechanisms of IAPP amyloid formation in vivo or in vitro are not understood and the mechanisms of IAPP induced β-cell death are not fully defined. Activation of the inflammasome, defects in autophagy, ER stress, generation of reactive oxygen species, membrane disruption, and receptor mediated mechanisms have all been proposed to play a role. Open questions in the field include the relative importance of the various mechanisms of β-cell death, the relevance of reductionist biophysical studies to the situation in vivo, the molecular mechanism of amyloid formation in vitro and in vivo, the factors which trigger amyloid formation in type-2 diabetes, the potential role of IAPP in type-1 diabetes, the development of clinically relevant inhibitors of islet amyloidosis toxicity, and the design of soluble, bioactive variants of IAPP for use as adjuncts to insulin therapy.





Author: Rehana Akter, Ping Cao, Harris Noor, Zachary Ridgway, Ling-Hsien Tu, Hui Wang, Amy G. Wong, Xiaoxue Zhang, Andisheh Abedin

Source: https://www.hindawi.com/



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