Study on the relationship between expression of islet amyloid polypeptide and onset of type 2 diabetes mellitus.

在2型糖尿病中，淀粉样蛋白沉积在胰岛内，而胰岛淀粉样蛋白被认为与该疾病的发生或进展有关。1987年，发现了胰岛淀粉样蛋白多肽（IAPP），它是胰岛淀粉样蛋白的主要成分。我们提出解决IAPP基因的表达与该疾病的发生或进展的关系。我们使用放射免疫测定系统测量了腹内侧损伤大鼠、肥胖Zucker大鼠和遗传性肥胖小鼠胰岛中IAPP的含量。肥胖和糖尿病动物体内IAPP含量升高。我们在一个新的胰腺β细胞系中观察到了IAPP的表达；从转基因小鼠胰岛素瘤中提取的MIN6。该细胞系可用于IAPP合成和分泌的研究。采用聚合酶链反应法对2型糖尿病患者IAPP基因5′-上游进行直接测序。在该区域观察到一个碱基多态性，但这种多态性与该病无关。我们成功生产了表达人IAPP的转基因小鼠。人类IAPP被证实在小鼠胰腺β细胞中特异性表达。该转基因小鼠将成为解决人类IAPP基因表达与2型糖尿病发病或进展关系的有效工具。

In type 2 diabetes mellitus, amyloid is deposited within pancreatic islets and insular amyloid has been thought to be related to onset or progression of this disease. In 1987, islet amyloid polypeptide (IAPP), a major component of this amyloid, was identified. We proposed to resolve the relationship between expression of IAPP gene and onset or progression of this disease. We measured IAPP content in the pancreatic islets of ventro-medial lesioned rats, obese Zucker rats and genetically obese mice, using a radioimmunoassay system. IAPP contents increased in these obese and diabetic animals. We observed expression of IAPP in a new pancreatic beta-cell line; MIN6 derived from transgenic mouse insulinoma. This cell line would be useful for study on IAPP synthesis and secretion. We examined 5'-upstream of IAPP gene of type 2 diabetic subjects by means of direct sequence using polymerase chain reaction. Polymorphism of one base in this region was observed, but this polymorphism was not related to this disease. We succeeded in the production of transgenic mouse expressing human IAPP. Human IAPP was confirmed to be specifically expressed in the pancreatic beta-cells of the mouse. The transgenic mouce should be a useful tool for resolving the relationship between expression of human IAPP gene and onset or progression of type 2 diabetes mellitus.