Kaneto Hideaki, Miyatsuka Takeshi, Kawamori Dan, Shiraiwa Toshihiko, Fujitani Yoshio, Matsuoka Taka-Aki
a Department of Internal Medicine and Therapeutics (A8), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Expert Rev Endocrinol Metab. 2006 Sep;1(5):587-600. doi: 10.1586/17446651.1.5.587.
Pancreatic and duodenal homeobox factor-1 (PDX-1) plays crucial roles in pancreas development and β-cell differentiation, and in maintaining mature β-cell function. MafA is a recently isolated β-cell-specific transcription factor that functions as a potent activator of insulin gene transcription. Also, these pancreatic transcription factors play a crucial role in inducing surrogate β-cells from non-β-cells and, thus, could be therapeutic targets for diabetes. Conversely, expression and/or activities of PDX-1 and MafA in β-cells are reduced under diabetic conditions, which leads to suppression of insulin biosynthesis and secretion. It is likely that alteration of such transcription factors explains, at least in part, the molecular mechanism for β-cell glucose toxicity.
胰腺十二指肠同源盒因子-1（PDX-1）在胰腺发育和β细胞分化以及维持成熟β细胞功能中发挥着关键作用。MafA是最近分离出的一种β细胞特异性转录因子，它作为胰岛素基因转录的有效激活剂发挥作用。此外，这些胰腺转录因子在从非β细胞诱导产生替代β细胞中起着关键作用，因此可能成为糖尿病的治疗靶点。相反，在糖尿病条件下，β细胞中PDX-1和MafA的表达和/或活性会降低，这导致胰岛素生物合成和分泌受到抑制。这些转录因子的改变很可能至少部分地解释了β细胞葡萄糖毒性的分子机制。
