Kaneto Hideaki, Miyatsuka Takeshi, Kawamori Dan, Matsuoka Taka-Aki
Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Rev Diabet Stud. 2007 Winter;4(4):209-25. doi: 10.1900/RDS.2007.4.209. Epub 2008 Feb 10.
It is well known that pancreatic and duodenal homeobox factor-1 (PDX-1) plays a pleiotropic role in the pancreas. In the developing pancreas, PDX-1 is involved in both pancreas formation and beta-cell differentiation. In mature beta-cells, PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and glucokinase. Furthermore, PDX-1 plays an important role in the induction of insulin-producing cells in various non-beta-cells and is thereby a possible therapeutic target for diabetes. On the other hand, under diabetic conditions, expression and/or activity of PDX-1 in beta-cells is reduced, which leads to suppression of insulin biosynthesis and secretion. It is likely that PDX-1 inactivation explains, at least in part, the molecular mechanism for beta-cell glucose toxicity found in diabetes.
众所周知，胰腺十二指肠同源盒因子-1（PDX-1）在胰腺中发挥着多效性作用。在胰腺发育过程中，PDX-1参与胰腺形成和β细胞分化。在成熟的β细胞中，PDX-1反式激活胰岛素及其他与β细胞相关的基因，如葡萄糖转运蛋白2（GLUT2）和葡萄糖激酶。此外，PDX-1在诱导各种非β细胞产生胰岛素的细胞中起重要作用，因此可能是糖尿病的治疗靶点。另一方面，在糖尿病条件下，β细胞中PDX-1的表达和/或活性降低，这导致胰岛素生物合成和分泌受到抑制。PDX-1失活可能至少部分解释了糖尿病中发现的β细胞葡萄糖毒性的分子机制。
