Type 2 diabetes (T2DM) is characterized by insulin resistance, defective insulin secretion, loss of beta-cell mass with increased beta-cell apoptosis and islet amyloid. The islet amyloid is derived from islet amyloid polypeptide (IAPP, amylin), a protein coexpressed and cosecreted with insulin by pancreatic beta-cells. In common with other amyloidogenic proteins, IAPP has the propensity to form membrane permeant toxic oligomers. Accumulating evidence suggests that these toxic oligomers, rather than the extracellular amyloid form of these proteins, are responsible for loss of neurons in neurodegenerative diseases. In this review we discuss emerging evidence to suggest that formation of intracellular IAPP oligomers may contribute to beta-cell loss in T2DM. The accumulated evidence permits the amyloid hypothesis originally developed for neurodegenerative diseases to be reformulated as the toxic oligomer hypothesis. However, as in neurodegenerative diseases, it remains unclear exactly why amyloidogenic proteins form oligomers in vivo, what their exact structure is, and to what extent these oligomers play a primary or secondary role in the cytotoxicity in what are now often called unfolded protein diseases.

中文翻译：

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2 型糖尿病中的胰岛淀粉样蛋白和毒性寡聚体假说。

2 型糖尿病 (T2DM) 的特征是胰岛素抵抗、胰岛素分泌缺陷、β 细胞量减少、β 细胞凋亡增加和胰岛淀粉样蛋白。胰岛淀粉样蛋白来源于胰岛淀粉样蛋白多肽（IAPP，胰淀素），这是一种由胰腺 β 细胞与胰岛素共表达和共分泌的蛋白质。与其他淀粉样蛋白一样，IAPP 具有形成膜渗透性毒性低聚物的倾向。越来越多的证据表明，这些有毒的低聚物，而不是这些蛋白质的细胞外淀粉样蛋白，是导致神经退行性疾病神经元丢失的原因。在这篇综述中，我们讨论了新出现的证据，表明细胞内 IAPP 寡聚体的形成可能导致 T2DM 中的 β 细胞丢失。积累的证据允许最初为神经退行性疾病开发的淀粉样蛋白假说重新表述为毒性寡聚体假说。然而，与神经退行性疾病一样，目前尚不清楚为什么淀粉样蛋白在体内形成寡聚体，它们的确切结构是什么，以及这些寡聚体在何种程度上在现在通常称为未折叠蛋白疾病的细胞毒性中发挥主要或次要作用。