Department of Chemistry, Stony Brook University, 100 Nicolls Road, Stony Brook, NY 11794-3400, United States.
Curr Opin Struct Biol. 2013 Feb;23(1):82-9. doi: 10.1016/j.sbi.2012.11.003. Epub 2012 Dec 22.
Amyloid formation in the pancreas by islet amyloid polypeptide (IAPP) leads to β-cell death and dysfunction, contributing to islet transplant failure and to type-2 diabetes. IAPP is stored in the β-cell insulin secretory granules and cosecreted with insulin in response to β-cell secretagogues. IAPP is believed to play a role in the control of food intake, in controlling gastric emptying and in glucose homeostasis. The polypeptide is natively unfolded in its monomeric state, but is one of the most amyloidogenic sequences known. The mechanisms of IAPP amyloid formation in vivo and in vitro are not understood; the mechanisms of IAPP induced cell death are unclear; and the nature of the toxic species is not completely defined. Recent work is shedding light on these important issues.
胰岛淀粉样多肽（IAPP）在胰腺中的淀粉样形成导致β细胞死亡和功能障碍，导致胰岛移植失败和 2 型糖尿病。IAPP 储存在β细胞胰岛素分泌颗粒中，并在β细胞分泌刺激物的作用下与胰岛素共同分泌。据信，IAPP 在控制食物摄入、控制胃排空和葡萄糖稳态方面发挥作用。该多肽在其单体状态下天然无折叠，但它是已知的最具淀粉样形成能力的序列之一。体内和体外 IAPP 淀粉样形成的机制尚不清楚；IAPP 诱导细胞死亡的机制尚不清楚；有毒物质的性质也不完全确定。最近的工作正在揭示这些重要问题。
