Although a large proportion of patients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown. Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas. Islet homogenates immunodepleted with anti-IAPP–specific antibodies were not able to induce IAPP aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose tolerance, and a substantial reduction on β cell number and mass. Finally, induction of IAPP deposition and diabetic abnormalities were also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic IAPP. Our findings suggest that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases.

尽管大部分2型糖尿病（T2D）患者积累了由胰岛淀粉样多肽（IAPP）组成的错误折叠的聚集体，但其在疾病中的作用尚不清楚。在这里，我们显示胰腺IAPP聚集体可以促进从转基因小鼠或健康人胰腺获得的胰岛培养物中内源性IAPP的错误折叠和聚集。用抗IAPP特异性抗体免疫消耗的胰岛匀浆不能诱导IAPP聚集。重要的是，将含有IAPP聚集体的胰匀浆腹膜内接种到表达人IAPP的转基因小鼠中可显着加速IAPP淀粉样蛋白沉积，并伴有T2D典型的临床异常，包括高血糖症，糖耐量降低以及β细胞数量和质量的显着降低。最后，通过施用使用纯的，合成的IAPP体外制​​备的IAPP聚集体，在体内也诱导了IAPP沉积和糖尿病异常的诱导。我们的发现表明，T2D的某些病理和临床改变可能通过through病毒在病毒疾病中传播的类似机制传播。