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Journal of Diabetes Research
Volume 2016, Article ID 5639875, 13 pages
http://dx.doi.org/10.1155/2016/5639875
Review Article

Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus

1Sorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, France
2Département de Chimie, Ecole Normale Supérieure, PSL Research University, 24 Rue Lhomond, 75005 Paris, France
3CNRS, UMR 7203 Laboratoire des Biomolécules, 75005 Paris, France

Received 27 November 2014; Accepted 3 March 2015

Academic Editor: Hiroshi Okamoto

Copyright © 2016 Lucie Caillon 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

Human islet amyloid polypeptide (hIAPP) is the major component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Mature hIAPP, a 37-aa peptide, is natively unfolded in its monomeric state but forms islet amyloid in T2DM. In common with other misfolded and aggregated proteins, amyloid formation involves aggregation of monomers of hIAPP into oligomers, fibrils, and ultimately mature amyloid deposits. hIAPP is coproduced and stored with insulin by the pancreatic islet β-cells and is released in response to the stimuli that lead to insulin secretion. Accumulating evidence suggests that hIAPP amyloid deposits that accompany T2DM are not just an insignificant phenomenon derived from the disease progression but that hIAPP aggregation induces processes that impair the functionality and the viability of β-cells. In this review, we particularly focus on hIAPP structure, hIAPP aggregation, and hIAPP-membrane interactions. We will also discuss recent findings on the mechanism of hIAPP-membrane damage and on hIAPP-induced cell death. Finally, the development of successful antiamyloidogenic agents that prevent hIAPP fibril formation will be examined.