Fox N, Schrementi J, Nishi M, Ohagi S, Chan S J, Heisserman J A, Westermark G T, Leckström A, Westermark P, Steiner D F
Department of Chemistry and Biotechnology Research, Lilly Research Labs, Lilly Corporate Center, Indianapolis, IN 46285.
FEBS Lett. 1993 May 24;323(1-2):40-4. doi: 10.1016/0014-5793(93)81444-5.
To model islet amyloidogenesis in NIDDM and explore the glucoregulatory role of islet amyloid polypeptide (IAPP), we have created transgenic mice containing a rat insulin-I promoter-human IAPP fusion gene. Expression of human IAPP was localized to the islets of Langerhans, anterior pituitary and brain in transgenic animals; blood IAPP levels were elevated 5-fold while fasting glucose levels remained normal. Amyloid deposits have not been detected in transgenic islets suggesting that other co-existing abnormalities in NIDDM may be required for the formation of islet amyloid. These animals provide a unique model for exploring this hypothesis and other proposed functions of IAPP.
为了模拟非胰岛素依赖型糖尿病(NIDDM)中的胰岛淀粉样变并探索胰岛淀粉样多肽(IAPP)的血糖调节作用,我们构建了含有大鼠胰岛素-I启动子-人IAPP融合基因的转基因小鼠。在转基因动物中,人IAPP的表达定位于胰岛、垂体前叶和脑;血液中IAPP水平升高了5倍,而空腹血糖水平仍保持正常。在转基因胰岛中未检测到淀粉样沉积物,这表明NIDDM中其他共存的异常情况可能是胰岛淀粉样变形成所必需的。这些动物为探索这一假说以及IAPP的其他假定功能提供了一个独特的模型。