Determinants of glucose toxicity and its reversibility in the pancreatic islet β-cell line, HIT-T15
Determinants of glucose toxicity and its reversibility in the pancreatic islet β-cell line, HIT-T15
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DOI：
10.1152/ajpendo.2000.279.5.e997
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发表时间：
2000-11-01
影响因子：
5.1
通讯作者：
Robertson, RP
中科院分区：
文献类型：
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作者：
Gleason, CE;Gonzalez, M;Robertson, RP
将克隆β细胞系HIT-T15细胞在含有各种浓度葡萄糖的RPMI 1640培养基中每周培养并传代6个月。中代和晚代细胞中的胰岛素含量下降是连续的而不是阈值葡萄糖浓度效应。在第二系列实验中，细胞在含有0.8或16.0 mM葡萄糖的培养基中从第76代至第105代生长。将在含16.0 mM葡萄糖的培养基中生长的第86、92和99代传代培养物转换为含0.8 mM葡萄糖的培养基，并继续传代至第105代。当在第86代和第92代进行转换时，观察到胰岛素含量和分泌以及胰岛素基因表达显著增加，但当在第99代进行转换时则没有。这些发现表明，胰岛素分泌细胞的葡萄糖毒性是一个连续的，而不是葡萄糖浓度的阈值函数，前期葡萄糖毒性的时间越短，越有可能发生细胞功能的完全恢复。
HIT-T15 cells, a clonal beta -cell line, were cultured and passaged weekly for 6 mo in RPMI 1640 media containing various concentrations of glucose. Insulin content decreased in the intermediate- and late-passage cells as a continuous rather than a threshold glucose concentration effect. In a second series of experiments, cells were grown in media containing either 0.8 or 16.0 mM glucose from passages 76 through 105. Subcultures of passages 86, 92, and 99 that had been grown in media containing 16.0 mM glucose were switched to media containing 0.8 mM glucose and also carried forward to passage 105. Dramatic increases in insulin content and secretion and insulin gene expression were observed when the switches were made at passages 86 and 92 but not when the switch was made at passage 99. These findings suggest that glucose toxicity of insulin-secreting cells is a continuous rather than a threshold function of glucose concentration and that the shorter the period of antecedent glucose toxicity, the more likely that full recovery of cell function will occur.