Serup P, Jensen J, Andersen F G, Jørgensen M C, Blume N, Holst J J, Madsen O D
Hagedorn Research Institute, Gentofte, Denmark.
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9015-20. doi: 10.1073/pnas.93.17.9015.
Insulin promoter factor 1 (IPF1), a member of the homeodomain protein family, serves an early role in pancreas formation, as evidenced by the lack of pancreas formation in mice carrying a targeted disruption of the IPF1 gene [Jonsson, J., Carlsson, L., Edlund, T. & Edlund, H. (1994) Nature (London) 371, 606-609]. In adults, IPF1 expression is restricted to the beta-cells in the islets of Langerhans. We report here that IPF1 induces expression of a subset of beta-cell-specific genes (insulin and islet amyloid polypeptide) when ectopically expressed in clones of transformed pancreatic islet alpha-cells. In contrast, expression of IPF1 in rat embryo fibroblasts factor failed to induce insulin and islet amyloid polypeptide expression. This is most likely due to the lack of at least one other essential insulin gene transcription factor, the basic helix-loop-helix protein Beta 2/NeuroD, which is expressed in both alpha- and beta-cells. We conclude that IPF1 is a potent transcriptional activator of endogenous insulin genes in non-beta islet cells, which suggests an important role of IPF1 in beta-cell maturation.
胰岛素启动子因子1（IPF1）是同源结构域蛋白家族的成员之一，在胰腺形成过程中发挥早期作用，携带IPF1基因靶向破坏的小鼠中缺乏胰腺形成就证明了这一点[琼森，J.，卡尔松，L.，埃德伦德，T. & 埃德伦德，H.（1994年）《自然》（伦敦）371，606 - 609]。在成年个体中，IPF1的表达局限于胰岛的β细胞。我们在此报告，当在转化的胰岛α细胞克隆中异位表达时，IPF1可诱导一部分β细胞特异性基因（胰岛素和胰岛淀粉样多肽）的表达。相比之下，在大鼠胚胎成纤维细胞中表达IPF1未能诱导胰岛素和胰岛淀粉样多肽的表达。这很可能是由于缺乏至少一种其他必需的胰岛素基因转录因子，即碱性螺旋 - 环 - 螺旋蛋白Beta 2/NeuroD，它在α细胞和β细胞中均有表达。我们得出结论，IPF1是胰岛非β细胞中内源性胰岛素基因的有效转录激活因子，这表明IPF1在β细胞成熟过程中发挥重要作用。
