Minami Kohtaro, Seino Susumu
Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Front Biosci. 2008 May 1;13:5824-37. doi: 10.2741/3119.
Although accumulating evidence indicates that proliferation of pre-existing beta-cells is the major mechanism of the maintenance of postnatal beta-cell mass, new beta-cells can be generated from non-beta-cells under certain conditions in vitro. We have recently shown directly by Cre/loxP-based cell lineage tracing that adult mouse pancreatic acinar cells can be transdifferentiated into insulin-secreting cells in vitro. These newly made cells secrete insulin in response to glucose and other secretagogues, but their secretory capacity is still low compared to that of native beta-cells. To improve the efficiency of generation of insulin-secreting cells from non-beta cells, it is critical to understand the molecular mechanism of such transdifferentiation. Since pancreatic acinar cells are the most abundant cell type in the pancreas, their utilization as a source of surrogate beta-cells is an intriguing approach to cell replacement therapy for type 1 diabetes. This review focuses on current knowledge of the regeneration of pancreatic beta-cells and transdifferentiation of pancreatic acinar-cells into insulin-secreting cells.
尽管越来越多的证据表明，已有的β细胞增殖是维持出生后β细胞量的主要机制，但在某些体外条件下，新的β细胞可由非β细胞生成。我们最近通过基于Cre/loxP的细胞谱系追踪直接表明，成年小鼠胰腺腺泡细胞在体外可转分化为胰岛素分泌细胞。这些新生成的细胞可响应葡萄糖和其他促分泌剂分泌胰岛素，但其分泌能力与天然β细胞相比仍然较低。为提高从非β细胞生成胰岛素分泌细胞的效率，了解这种转分化的分子机制至关重要。由于胰腺腺泡细胞是胰腺中最丰富的细胞类型，将其用作替代β细胞的来源是1型糖尿病细胞替代治疗的一种有趣方法。本综述重点关注胰腺β细胞再生以及胰腺腺泡细胞转分化为胰岛素分泌细胞的当前知识。
