Kaneto Hideaki, Matsuoka Taka-aki, Katakami Naoto, Matsuhisa Munehide
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Curr Med Chem. 2009;16(24):3144-51. doi: 10.2174/092986709788802980.
A decrease in the number of functioning pancreatic beta-cells and insufficient insulin biosynthesis and/or secretion are the hallmarks of diabetes. Therefore, the identification of alternative sources to induce insulin-producing surrogate beta-cells is of great importance. For the induction of insulin-producing cells from various cells and/or tissues, it is useful to mimic and reproduce expression alterations of various pancreatic transcription factors observed during normal pancreas development and to induce key pancreatic transcription factors which have the potency to induce insulin and other beta-cell-related genes. MafA, PDX-1 and NeuroD directly bind to the insulin gene promoter and function as very important transcription factors in pancreatic beta-cell differentiation and mature beta-cell function. The combination of MafA, PDX-1 and NeuroD markedly induces insulin biosynthesis in various non-beta-cells and thereby is a useful tool to efficiently induce insulin-producing surrogate beta-cells.
功能性胰腺β细胞数量减少以及胰岛素生物合成和/或分泌不足是糖尿病的标志。因此，确定诱导产生胰岛素的替代β细胞来源至关重要。为了从各种细胞和/或组织诱导产生胰岛素的细胞，模拟和重现正常胰腺发育过程中观察到的各种胰腺转录因子的表达变化，并诱导具有诱导胰岛素和其他β细胞相关基因能力的关键胰腺转录因子是很有用的。MafA、PDX-1和NeuroD直接结合胰岛素基因启动子，并在胰腺β细胞分化和成熟β细胞功能中作为非常重要的转录因子发挥作用。MafA、PDX-1和NeuroD的组合能显著诱导各种非β细胞中的胰岛素生物合成，因此是有效诱导产生胰岛素的替代β细胞的有用工具。
