Variable regulation by insulin of insulin gene expression in HIT-T15 cells.
Variable regulation by insulin of insulin gene expression in HIT-T15 cells.
复制标题
胰岛素对 HIT-T15 细胞中胰岛素基因表达的可变调节。
DOI：
10.1007/bf00403373
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发表时间：
1994
期刊：
影响因子：
8.2
通讯作者：
Robertson,RP
中科院分区：
文献类型：
--
作者：
Zhang,HJ;Petersen,B;Robertson,RP
葡萄糖和胰岛素通常被认为对胰岛的胰岛素合成和分泌有相反的作用。在很大程度上，这种概括是从短期实验中产生的。我们的研究集中在胰岛素浓度变化对HIT-T15细胞胰岛素基因表达和分泌的慢性、长期影响。从传代70开始，HIT细胞分裂，每周在含11.1 mmol/l葡萄糖的培养基中传代25周，不添加胰岛素；(B) 11.1 mmol/l葡萄糖加胰岛素维持在4000 μU/ml左右；(C) 0.8 mmol/l葡萄糖，不添加胰岛素；(D) 0.8 mmol/l葡萄糖加胰岛素维持在4000 μU/ml左右；(E) 0.8 mmol/l葡萄糖，随着时间的推移逐渐减少胰岛素的添加，以模拟条件a中培养基中胰岛素水平的逐渐下降。我们的数据表明，在HIT细胞的慢性传递过程中，外源性胰岛素的添加导致11.1 mmol/l葡萄糖培养基中培养的细胞中胰岛素mRNA、胰岛素含量和胰岛素分泌水平保持不变。而在葡萄糖浓度为0.8 mmol/l的培养基中，胰岛素的加入降低了胰岛素mRNA水平、胰岛素含量和胰岛素分泌。尽管如此，在所有情况下，外源性添加胰岛素维持更高水平的胰岛素mRNA、胰岛素含量和胰岛素分泌，而不是只使用含有高浓度葡萄糖的培养基。这些结果表明，评估胰岛素对β细胞功能影响的短期实验不一定适用于慢性的、更长期的实验，在这些实验中，胰岛素对胰岛素基因表达和分泌具有可变的时间和浓度依赖性。
Glucose and insulin are generally considered to express opposite effects on insulin synthesis and secretion from pancreatic islets. For the most part this generalization has arisen from short-term experiments. Our studies focused on the chronic, long-term effects of variable insulin concentrations on insulin gene expression and secretion in cultures of HIT-T15 cells. From passage 70, HIT cells were split and passed weekly for 25 weeks in media containing either (A) 11.1 mmol/l glucose with no insulin added; (B) 11.1 mmol/l glucose with insulin added to maintain a level of approximately 4,000 μU/ml; (C) 0.8 mmol/l glucose with no insulin added; (D) 0.8 mmol/l glucose with insulin added to maintain a level of approximately 4,000 μU/ml; and (E) 0.8 mmol/l glucose with progressively less insulin added over time to mimic the gradual decrease in media insulin levels found in condition A. Our data indicate that during chronic passing of HIT cells, addition of exogenous insulin led to preserved levels of insulin mRNA, insulin content and insulin secretion in cells cultured in media containing 11.1 mmol/l glucose concentration. However, in media containing 0.8 mmol/l glucose concentration, addition of insulin diminished the levels of insulin mRNA, insulin content and insulin secretion. Nonetheless, in all cases exogenously added insulin sustained greater levels of insulin mRNA, insulin content and insulin secretion than the instance wherein media containing a high concentration of glucose only was used. These results indicate that short-term experiments assessing the effects of insulin on beta-cell function do not necessarily apply to chronic, more long-term experiments in which insulin can have variable time- and concentration-dependent effects on insulin gene expression and secretion.