小鼠Ipf1/Pdx1基因的β细胞特异性失活导致β细胞表型丧失和成年型糖尿病。
beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes.
作者信息
Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H
机构信息
Department of Microbiology, University of Umeâ, S-901 87 Umeâ, Sweden.
出版信息
Genes Dev. 1998 Jun 15;12(12):1763-8. doi: 10.1101/gad.12.12.1763.
Abstract
To study the late beta-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted specifically in beta cells. These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-dependent manner suggesting that lowered IPF1/PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin.
摘要
为了研究同源结构域蛋白IPF1/PDX1在晚期β细胞中的特异性功能，我们构建了Ipf1/Pdx1基因在β细胞中特异性缺失的小鼠。这些小鼠随年龄增长会患糖尿病，并且我们发现IPF1/PDX1通过正向调节胰岛素和胰岛淀粉样多肽的表达以及抑制胰高血糖素的表达来维持β细胞的特性。我们还提供证据表明，IPF1/PDX1以剂量依赖的方式调节Glut2的表达，这表明IPF1/PDX1活性降低可能通过导致Glut2和胰岛素表达受损而促成II型糖尿病的发生。
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