title: Molecular Structure, Membrane Interactions, and Toxicity of the Islet Amyloid Polypeptide in Type 2 Diabetes Mellitus.
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.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, France ; Département de Chimie, Ecole Normale Supérieure, PSL Research University, 24 Rue Lhomond, 75005 Paris, France ; CNRS, UMR 7203 Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Caillon
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, France ; Département de Chimie, Ecole Normale Supérieure, PSL Research University, 24 Rue Lhomond, 75005 Paris, France ; CNRS, UMR 7203 Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Anais R F
authors.initials: AR
authors.lastname: Hoffmann
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, France ; Département de Chimie, Ecole Normale Supérieure, PSL Research University, 24 Rue Lhomond, 75005 Paris, France ; CNRS, UMR 7203 Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Botz
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, Laboratoire des Biomolécules, 4 Place Jussieu, 75005 Paris, France ; Département de Chimie, Ecole Normale Supérieure, PSL Research University, 24 Rue Lhomond, 75005 Paris, France ; CNRS, UMR 7203 Laboratoire des Biomolécules, 75005 Paris, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Khemtemourian
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D015394:Molecular Structure
chemical_list: D058228:Islet Amyloid Polypeptide