Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes.
Detrimental effect of protracted hyperglycaemia on beta-cell neogenesis in a mouse murine model of diabetes.
复制标题
长期高血糖对糖尿病小鼠模型中β细胞新生的不利影响。
DOI：
10.1007/s00125-002-0970-y
复制
发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Teitelman,G
中科院分区：
文献类型：
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作者：
Guz,Y;Torres,A;Teitelman,G
AbstractAims /假说。先前的研究表明，在注射高剂量的β细胞毒素链脲佐菌素诱导糖尿病的小鼠胰岛中，新的β细胞从胰岛内前体分化出来。此外，胰岛素治疗在链脲佐菌素治疗后1天重建血糖改善了再生过程。我们试图评估延迟1周血糖恢复是否会影响β细胞再生。方法：成年CD-1小鼠注射200 mg/kg链脲佐菌素。一组小鼠在整个实验过程中保持高血糖，而另一组小鼠在注射链脲佐菌素1周后给予胰岛素治疗后血糖正常。结果：链脲佐菌素治疗后，正常血糖恢复后小鼠胰岛内出现新的β细胞。与链脲佐菌素治疗后血糖浓度迅速恢复的小鼠胰岛一样，链脲佐菌素治疗后1周血糖正常的小鼠胰岛也有两种潜在的胰岛素前体细胞类型。然而，持续的高血糖对胰岛素细胞新生有一些有害的影响，如成功再生β细胞的血糖小鼠数量减少，新分化的含胰岛素细胞数量和存活率降低。这些结果表明，当胰岛长时间暴露于高循环葡萄糖浓度时，它们逐渐失去再生潜力。
AbstractAims/hypothesis.Previous studies have shown that new beta cells differentiate from intra-islet precursors in pancreatic islets of mice in which diabetes is induced by injecting a high dose of the beta-cell toxin streptozotocin. Moreover, the re-establishment of euglycaemia by insulin therapy 1 day after streptozotocin treatment improved the process of regeneration. We sought to assess whether a 1-week delay in the restoration of euglycaemia would affect beta-cell regeneration.Methods.Adult CD-1 mice were injected with 200 mg/kg of streptozotocin. One group of mice remained hyperglycaemic throughout the experiment while a second group became normoglycaemic following the administration of insulin therapy 1 week after the injection of streptozotocin. Pancreata removed at different times after treatment were processed for visualization ofβ precursor-cell markers and insulin by confocal microscopy.Results.New beta cells appeared in islets of streptozotocin-treated mice after restoration of normoglycaemia. Like islets of streptozotocin mice in which blood glucose concentrations were rapidly restored, islets of mice that became normoglycaemic 1 week after streptozotocin treatment also had two potential insulin precursor cell types. Protracted hyperglycaemia however, had several harmful effects on insulin cell neogenesis, such as a reduction in the number of euglycaemic mice with successful beta-cell regeneration and a decrease in the number and survival of the newly differentiated insulin-containing cells.Conclusion/interpretation.These results indicate that islets gradually lose their regenerative potential when they are exposed to high circulating glucose concentrations for an extended period of time.