胰岛淀粉样多肽的研究进展

由蛋白错误折叠后聚集所产生的淀粉样蛋白沉积是导致老年痴呆症、疯牛病、2型糖尿病等多种疾病的重要因素。由胰岛淀粉样多肽(islet amyloid polypeptide,IAPP)所形成的淀粉样蛋白沉积,具有破坏胰岛β细胞膜结构、诱导β细胞凋亡和损伤β细胞功能的作用,被认为是2型糖尿病的重要致病原因之一。对IAPP的聚集性、聚集体的结构,以及其对β细胞的毒性作用研究,不但有助于明确2型糖尿病的发病机制,而且最新研究也表明抑制IAPP的聚集可有效减少β细胞的凋亡,提高胰岛移植的成功率。因此,IAPP已成为2型糖尿病治疗中一个具有良好前景的靶点。该文对IAPP研究的最新进展进行了简要介绍。

Recent progress of islet amyloid polypeptide

Amyloid protein and depositions formed by misfolded proteins have been identified in multiple diseases, including Alzheimer’s disease mad cow disease, and were considered as an important causative factor of these diseases. In type 2 diabetes, the misfolded islet amyloid polypeptide （IAPP） was identified as the major component of amyloid deposition identified in the autopsy samples of patients’ islets of Langerhans. Studies in vivo and in vitro suggested that IAPP can disturb the integrity of β cell membrane, induce β-cell apoptosis and damage β-cell function, and was thus considered as one of the important causative factors of type 2 diabetes. The molecular pathogenesis of type 2 diabetes can be elucidated via studying the mechanisms of IAPP aggregation, multiple IAPP aggregation forms and their respective structures, and its β cell toxicity. On the other hand, inhibition of IAPP aggregation has been proven effectively reducing the β-cell apoptosis and ensuring the success of pancreas transplantation, thus making IAPP a potential therapeutic target of type 2 diabetes. In the present review, the latest progresses on the aggregation of IAPP were summarized.