Diabetes Transplant Unit, Prince of Wales Hospital, Sydney, New South Wales, Australia.
Islets. 2009 Jul-Aug;1(1):55-61. doi: 10.4161/isl.1.1.8993.
NeuroD (BETA2), a bHLH transcription factor is known to be involved in early pancreatic endocrine as well as neuronal differentiation. NeuroD is known to regulate distinct sets of molecules that are important for survival and differentiation of pancreatic cells. We assessed whether forced expression of NeuroD, can induce maturation of FAO-ins liver cells to β-like cells. To test this we stably transfected NeuroD into these cells that constitutively secrete insulin. Transfected cells showed enhanced expression of preproinsulin mRNA, elevated insulin content and cumulative insulin secretion. There was an up-regulation of expression of the genes for the transcription factor Foxa2, L-type Ca2+ channels subunit α 1C and α 1D and secretory granular protein chromogranin A. These FAO-ins-hNd cells show increased insulin secretion in response to calcium and theophylline, but not glucose. However, secretion of insulin remained constitutive rather than regulated. These studies demonstrate that NeuroD alone may not be sufficient to induce regulated insulin release in insulin-producing liver cells.
神经源性分化因子（NeuroD）（BETA2）是一种 bHLH 转录因子，已知其参与早期胰腺内分泌和神经元分化。NeuroD 已知可调节对胰腺细胞存活和分化很重要的不同分子。我们评估了强制表达 NeuroD 是否可以诱导 FAO-ins 肝细胞向 β 样细胞成熟。为了测试这一点，我们将 NeuroD 稳定转染到这些持续分泌胰岛素的细胞中。转染细胞显示出 preproinsulin mRNA 的表达增强，胰岛素含量升高和累积胰岛素分泌增加。转录因子 Foxa2、L 型 Ca2+通道亚基α1C 和α1D 以及分泌颗粒蛋白嗜铬粒蛋白 A 的表达上调。这些 FAO-ins-hNd 细胞对钙和茶碱的胰岛素分泌增加，但对葡萄糖没有反应。然而，胰岛素分泌仍然是组成性的而不是受调节的。这些研究表明，仅 NeuroD 可能不足以诱导胰岛素产生的肝细胞中受调节的胰岛素释放。
