Yamaoka T, Yoshino K, Yamada T, Idehara C, Hoque M O, Moritani M, Yoshimoto K, Hata J, Itakura M
Division of Genetic Information, Institute for Genome Research, University of Tokushima, Japan.
Biochem Biophys Res Commun. 2000 Nov 19;278(2):368-76. doi: 10.1006/bbrc.2000.3813.
To examine the effect of overexpressed regenerating gene (Reg) I on pancreatic beta-cells, we generated transgenic mice expressing Reg I in islets (Reg-Tg mice). Three lines of Reg-Tg mice were established. In line-1 Reg-Tg mice, the expression level of Reg I mRNA in islets was 7 times higher than those in lines 2 and 3 of Reg-Tg mice, and line 1 mice developed diabetes by apoptosis of beta-cells, as well as various malignant tumors. In addition to the decrease in beta-cells, compensatory islet regeneration and proliferation of ductal epithelial cells were observed in line-1 Reg-Tg mice. Because Reg I protein was secreted primarily into pancreatic ducts from acinar cells, it may primarily stimulate the proliferation of ductal epithelial cells, and not beta-cells, and their differentiation into islets. Moreover, the tumor-promoting activity of Reg I protein should be considered for its possible clinical applications.
为了研究过表达再生基因（Reg）I对胰腺β细胞的影响，我们构建了胰岛中表达Reg I的转基因小鼠（Reg-Tg小鼠）。建立了3个品系的Reg-Tg小鼠。在1号线Reg-Tg小鼠中，胰岛中Reg I mRNA的表达水平比2号线和3号线Reg-Tg小鼠高7倍，1号线小鼠因β细胞凋亡以及各种恶性肿瘤而发生糖尿病。除了β细胞减少外，在1号线Reg-Tg小鼠中还观察到代偿性胰岛再生和导管上皮细胞增殖。由于Reg I蛋白主要从腺泡细胞分泌到胰腺导管中，它可能主要刺激导管上皮细胞的增殖，而非β细胞，以及它们向胰岛的分化。此外，Reg I蛋白的促肿瘤活性在其可能的临床应用中应予以考虑。
