title: Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology.
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.
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Rehana
authors.initials: R
authors.lastname: Akter
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Harris
authors.initials: H
authors.lastname: Noor
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Ridgway
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Ling-Hsien
authors.initials: LH
authors.lastname: Tu
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Amy G
authors.initials: AG
authors.lastname: Wong
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Diabetes Research Program, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Andisheh
authors.initials: A
authors.lastname: Abedini
authors.affiliation: Diabetes Research Program, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA ; Research Department of Structural and Molecule Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Raleigh
mesh_terms: 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*; D013329:Structure-Activity Relationship
chemical_list: D058228:Islet Amyloid Polypeptide