Matsuoka Taka-aki, Artner Isabella, Henderson Eva, Means Anna, Sander Maike, Stein Roland
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 723 Light Hall, Nashville, TN 37232, USA.
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2930-3. doi: 10.1073/pnas.0306233101. Epub 2004 Feb 18.
Insulin gene expression is regulated by several islet-enriched transcription factors. However, MafA is the only beta cell-specific activator. Here, we show that MafA selectively induces endogenous insulin transcription in non-beta cells. MafA was also first detected in the insulin-producing cells formed during the second and predominant phase of beta cell differentiation, and absent in the few insulin-positive cells found in Nkx6.1(-/-) pancreata, which lack the majority of second-phase beta cells. These results demonstrate that MafA is a potent insulin activator that is likely to function downstream of Nkx6.1 during islet insulin-producing cell development.
胰岛素基因表达受多种胰岛富集转录因子调控。然而,MafA是唯一的β细胞特异性激活因子。在此,我们表明MafA可在非β细胞中选择性诱导内源性胰岛素转录。MafA也首次在β细胞分化的第二个主要阶段形成的胰岛素生成细胞中被检测到,而在缺乏大多数第二阶段β细胞的Nkx6.1(-/-)胰腺中发现的少数胰岛素阳性细胞中不存在。这些结果表明,MafA是一种有效的胰岛素激活因子,在胰岛胰岛素生成细胞发育过程中可能在Nkx6.1的下游发挥作用。