Nagamatsu S, Nishi M, Steiner D F
Department of Biochemistry(II), Kyorin University School of Medicine, Tokyo, Japan.
Diabetes Res Clin Pract. 1992 Jan;15(1):49-55. doi: 10.1016/0168-8227(92)90067-2.
Effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion were examined in isolated rat islets and mouse beta TC3 cells. Culture of islets or mouse beta TC3 cells for 24 h in the presence of 10(-6) M IAPP and 5.5 mM glucose had no effect on insulin mRNA levels. The rates of proinsulin biosynthesis were not altered in islets incubated in 10(-4)-10(-9) M IAPP. In beta TC3 cells, proinsulin biosynthesis was stimulated by glucose, though no effects of IAPP were shown. Addition of 10(-5) M IAPP to islets incubated in 11 mM glucose decreased the fractional insulin secretion rates; however, the secretion of insulin from beta TC3 cells was not affected by 10(-5) M IAPP. On the other hand, mouse beta TC3 cells expressed the elevated level of IAPP mRNA. Metabolic labeling of beta TC3 cells revealed the synthesis of both proIAPP and mature IAPP. In pulse chase experiments, proIAPP was processed to IAPP in a manner similar to proinsulin. These data indicate that IAPP is a possible polypeptide hormone synthesized in pancreatic beta cells though it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion.
在分离的大鼠胰岛和小鼠β TC3细胞中检测了大鼠胰岛淀粉样多肽（IAPP）对胰岛素生物合成和分泌的影响。在10^(-6) M IAPP和5.5 mM葡萄糖存在的情况下，将胰岛或小鼠β TC3细胞培养24小时对胰岛素mRNA水平没有影响。在10^(-4)-10^(-9) M IAPP中孵育的胰岛中，胰岛素原生物合成速率没有改变。在β TC3细胞中，葡萄糖刺激胰岛素原生物合成，尽管未显示IAPP的作用。向在11 mM葡萄糖中孵育的胰岛中添加10^(-5) M IAPP会降低胰岛素分泌分数率；然而，10^(-5) M IAPP对β TC3细胞的胰岛素分泌没有影响。另一方面，小鼠β TC3细胞中IAPP mRNA水平升高。β TC3细胞的代谢标记显示了胰岛素原性IAPP和成熟IAPP的合成。在脉冲追踪实验中，胰岛素原性IAPP以类似于胰岛素原的方式加工成IAPP。这些数据表明，IAPP是一种可能在胰腺β细胞中合成的多肽激素，尽管IAPP不太可能是胰岛素生物合成或分泌的生理相关调节剂。
