Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology.
Islet Amyloid Polypeptide: Structure, Function, and Pathophysiology.
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DOI：
10.1155/2016/2798269
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发表时间：
2016
影响因子：
4.3
通讯作者：
Raleigh DP
中科院分区：
文献类型：
--
作者：
Akter R;Cao P;Noor H;Ridgway Z;Tu LH;Wang H;Wong AG;Zhang X;Abedini A;Schmidt AM;Raleigh DP
激素胰岛淀粉样多肽（IAPP 或胰淀素）在葡萄糖稳态中发挥作用，但在 2 型糖尿病中聚集形成胰岛淀粉样蛋白。胰岛淀粉样蛋白的形成导致疾病中的β细胞功能障碍和死亡以及胰岛移植的失败。最近的研究表明 IAPP 聚集在 2 型糖尿病心血管并发症中发挥作用，并暗示其在 1 型糖尿病中可能发挥作用。 IAPP 淀粉样蛋白在体内或体外形成的机制尚不清楚，IAPP 诱导 β 细胞死亡的机制尚未完全明确。炎症小体的激活、自噬缺陷、内质网应激、活性氧的产生、膜破坏和受体介导机制都被认为发挥了作用。该领域的悬而未决的问题包括β细胞死亡的各种机制的相对重要性、还原论生物物理研究与体内情况的相关性、体外和体内淀粉样蛋白形成的分子机制、触发2型糖尿病中淀粉样蛋白形成的因素、IAPP在1型糖尿病中的潜在作用、胰岛淀粉样变性毒性的临床相关抑制剂的开发，以及用作胰岛素治疗辅助剂的IAPP的可溶性生物活性变体的设计。
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.