Islet amyloid: From fundamental biophysics to mechanisms of cytotoxicity

• Published in: FEBS letters Vol. 587; no. 8; pp. 1106 - 1118
• Main Authors: Cao, Ping, Marek, Peter, Noor, Harris, Patsalo, Vadim, Tu, Ling-Hsien, Wang, Hui, Abedini, Andisheh, Raleigh, Daniel P.
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 17.04.2013
• Subjects: Amino Acid Sequence; Amylin; Amyloid; Amyloid - chemistry; Amyloid - genetics; Amyloid - metabolism; Biophysical Phenomena; Cell Survival; Humans; IAPP; Islet amyloid polypeptide; Islet Amyloid Polypeptide - chemistry; Islet Amyloid Polypeptide - genetics; Islet Amyloid Polypeptide - metabolism; Models, Molecular; Molecular Sequence Data; Mutation; Protein Structure, Secondary; Sequence Homology, Amino Acid; Type 2 diabetes; Type 2 diabetes; Amyloid; IAPP; Islet amyloid polypeptide; Amylin
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2013.01.046

Pancreatic islet amyloid is a characteristic feature of type 2 diabetes. The major protein component of islet amyloid is the polypeptide hormone known as islet amyloid polypeptide (IAPP, or amylin). IAPP is stored with insulin in the β-cell secretory granules and is released in response to the stimuli that lead to insulin secretion. IAPP is normally soluble and is natively unfolded in its monomeric state, but forms islet amyloid in type 2 diabetes. Islet amyloid is not the cause of type 2 diabetes, but it leads to β-cell dysfunction and cell death, and contributes to the failure of islet cell transplantation. The mechanism of IAPP amyloid formation is not understood and the mechanisms of cytotoxicity are not fully defined.