Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe.
Division of Cellular and Molecular Medicine, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe ; Department of Autonomic Physiology, Graduate School of Medicine, Chiba University, Chiba.
J Diabetes Investig. 2010 Aug 2;1(4):137-42. doi: 10.1111/j.2040-1124.2010.00026.x.
Incretin/cyclic adenosine monophosphate (cAMP) signaling is critical for potentiation of insulin secretion. Although several cell lines of pancreatic β-cells are currently available, there are no cell lines suitable for investigation of incretin/cAMP signaling. In the present study, we have newly established pancreatic β-cell lines (named MIN6-K) from the IT6 mouse, which develops insulinoma. MIN6-K8 cells respond to both glucose and incretins, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), as is the case in pancreatic islets, whereas MIN6-K20 cells respond to glucose, but not to incretins. Despite the difference in incretin-potentiated insulin secretion between these two cell lines, the accumulation of cAMP after stimulation of GLP-1 is comparable in these cells. Interestingly, we also found that incretin responsiveness is drastically induced by the formation of pseudoislets from MIN6-K20 cells to a level comparable to that of pancreatic islets. Thus, these cell lines are useful for studying incretin/cAMP signaling in β-cells. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00026.x, 2010).
胰岛素/环腺苷酸 (cAMP) 信号通路对于增强胰岛素分泌至关重要。尽管目前已有几种胰腺 β 细胞系,但尚无适合研究肠促胰岛素/cAMP 信号通路的细胞系。本研究中,我们从 IT6 小鼠中建立了新的胰腺 β 细胞系(命名为 MIN6-K),该小鼠可发展为胰岛素瘤。MIN6-K8 细胞对葡萄糖和肠促胰岛素(如胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性胰岛素释放肽(GIP))均有反应,这与胰腺胰岛的情况相同,而 MIN6-K20 细胞仅对葡萄糖有反应,而对肠促胰岛素无反应。尽管这两种细胞系在肠促胰岛素增强的胰岛素分泌方面存在差异,但 GLP-1 刺激后 cAMP 的积累在这些细胞中是相当的。有趣的是,我们还发现,MIN6-K20 细胞形成假胰岛后,肠促胰岛素的反应性会急剧增强,达到与胰腺胰岛相当的水平。因此,这些细胞系可用于研究 β 细胞中的肠促胰岛素/cAMP 信号通路。(《糖尿病研究与临床实践》,doi: 10.1111/j.2040-1124.2010.00026.x,2010)。