Regeneration of pancreatic β cells from intra-islet precursor cells in an experimental model of diabetes
Regeneration of pancreatic β cells from intra-islet precursor cells in an experimental model of diabetes
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DOI：
10.1210/en.142.11.4956
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发表时间：
2001-11-01
期刊：
影响因子：
4.8
通讯作者：
Teitelman, G
中科院分区：
文献类型：
--
作者：
Guz, Y;Nasir, I;Teitelman, G
我们以前报道过，在注射高剂量β细胞毒素链脲佐菌素（SZ）导致糖尿病的小鼠胰岛中，新的β细胞分化，这种β细胞毒素由于快速和大量的β细胞死亡而产生高血糖。在sz介导的现有β细胞消除后，含有胰岛素的细胞群在胰岛中重新出现。然而，新β细胞的数量很少，而且这些动物仍然处于严重的高血糖状态。在本研究中，我们测试了外源性胰岛素恢复正常血糖是否会促进β细胞分化和成熟。我们发现sz治疗的小鼠在胰岛素给药后迅速达到正常血糖水平，β细胞再生得到改善，因为在正常血糖恢复后的第一周，每个胰岛的β细胞数量达到了对照组的近40%。再生胰岛中出现了两种假定的前体细胞类型。一种细胞表达葡萄糖转运蛋白-2 (Glut-2)，另一种细胞共表达胰岛素和生长抑素。这些细胞可能产生了含有胰岛素的单特异性细胞，这些细胞重新填充了胰岛。我们得出结论，β细胞新生发生在成人胰岛，这一过程的结果受到胰岛素介导的循环血糖水平正常化的调节。
We previously reported that new beta cells differentiated in pancreatic islets of mice in which diabetes was produced by injection of a high dose of the beta cell toxin streptozotocin (SZ), which produces hyperglycemia due to rapid and massive beta cell death. After SZ-mediated elimination of existing beta cells, a population of insulin containing cells reappeared in islets. However, the number of new beta cells was small, and the animals remained severely hyperglycemic. In the present study, we tested whether restoration of normoglycemia by exogenous administered insulin would enhance beta cell differentiation and maturation. We found that beta cell regeneration improved in SZ-treated mice animals that rapidly attained normoglycemia following insulin administration because the number of beta cells per islet reached near 40% of control values during the first week after restoration of normoglycemia. Two presumptive precursor cell types appeared in regenerating islets. One expressed the glucose transporter-2 (Glut-2), and the other cell type coexpressed insulin and somatostatin. These cells probably generated the monospecific cells containing insulin that repopulated the islets. We conclude that beta cell neogenesis occurred in adult islets and that the outcome of this process was regulated by the insulin-mediated normalization of circulating blood glucose levels.