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，胰岛淀粉样蛋白被认为与疾病的发生或发展有关。1987年，胰岛淀粉样多肽(IAPP)被鉴定出来，它是这种淀粉样蛋白的主要成分。我们建议解决IAPP基因表达与本病发生发展的关系。我们用放射免疫分析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。这些肥胖和糖尿病动物的IAPP含量增加。我们观察到IAPP在一种新的胰岛β细胞系MIN6中的表达，该细胞系来源于转基因小鼠胰岛素瘤。该细胞系可用于研究IAPP的合成和分泌。用聚合酶链式反应直接测序的方法检测了2型糖尿病患者IAPP基因的5‘-上游。观察到该区域一个碱基的多态，但该多态与本病无关。我们成功地制备了表达人IAPP的转基因小鼠。人IAPP被证实在小鼠的胰岛β细胞中特异表达。该转基因小鼠有望成为解决人IAPP基因表达与2型糖尿病发生发展关系的有效工具。

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.