Mechanisms of functional expression of pancreatic islets as an integrated system and its failure

我们新建立了胰腺b细胞系（命名为MIN6-K）。在单层培养中，MIN6-K8细胞对葡萄糖刺激和camp增加剂（如肠促胰岛素激素）均有反应，而MIN6-K20细胞对葡萄糖刺激有反应，但对肠促胰岛素没有反应。我们发现MIN6-K20细胞（假胰岛）的三维结构的形成急剧诱导cAMP/肠促胰岛素反应到与正常胰岛相似的水平。我们还发现胰腺腺泡细胞在体外转分化为b细胞需要三维结构的形成。这些发现表明，胰腺b细胞的三维结构在胰岛素分泌的正常调节中作为一个综合系统的发展至关重要。

We have newly established pancreatic b-cell lines(named MIN6-K). In monolayer culture, MIN6-K8 cells respond to both glucose stimulation and cAMP-increasing agents such as the incretin hormones, while MIN6-K20 cells respond to glucose stimulation, but not to incretins. We found that the formation of three-dimensional structure of MIN6-K20 cells(pseudoislets) drastically induces cAMP/incretin responsiveness to a level similar to that of normal pancreatic islets. We also found that formation of three-dimensional structure is required for transdifferentiation of pancreatic acinar cells to b-cells in vitro. These findings indicate that three-dimensional structure of pancreatic b-cells is critical in development of normal regulation of insulin secretion as an integrative system.