Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment
Recovery from diabetes in neonatal mice after a low-dose streptozotocin treatment
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DOI：
10.1016/j.bbrc.2012.12.030
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发表时间：
2013-01-18
影响因子：
3.1
通讯作者：
Kume, Shoen
中科院分区：
文献类型：
--
作者：
Kataoka, Masateru;Kawamuro, Yuki;Kume, Shoen
链脲佐菌素（STZ）的施用诱导β细胞的破坏，并且被广泛用作I型糖尿病的实验动物模型。在新生大鼠中，低剂量STZ介导的β细胞破坏后，β细胞再生发生，并观察到高血糖的逆转。然而，在新生小鼠中，β细胞再生似乎比在大鼠中观察到的要慢得多。在这里，我们描述了在低剂量STZ小鼠模型中诱导的糖尿病自发缓慢恢复期间β细胞质量的时间依赖性定量变化。然后，我们研究了潜在的机制，并分析了β细胞恢复的细胞来源。我们在此表明，出生后第7天（P7）用50 mg/kg STZ处理的雌性小鼠经历了大部分β细胞的破坏，并出现高血糖症。血糖逐渐升高，并在第35-50天达到峰值水平500 mg/dl。随后是β细胞的自发再生。在150天内观察到非空腹血糖逆转至对照值。然而，小鼠在第150天和第220天仍然显示葡萄糖耐量受损，尽管在第150天观察到显著改善。β-细胞质量的定量显示，β-细胞质量在第100天和第150天之间显著增加。在第150天和第220天，β细胞质量分别约为对照的23%和48.5%。在胰岛素阳性细胞中，10%为PCNA阳性增殖细胞。我们的研究结果表明，β细胞复制是β细胞再生的细胞来源之一。(C)2012 Elsevier Inc. All rights reserved.
Administration of streptozotocin (STZ) induces destruction of beta-cells and is widely used as an experimental animal model of type I diabetes. In neonatal rat, after low-doses of STZ-mediated destruction of beta-cells, beta-cells regeneration occurs and reversal of hyperglycemia was observed. However, in neonatal mice, beta-cell regeneration seems to occur much slowly compared to that observed in the rat. Here, we described the time dependent quantitative changes in beta-cell mass during a spontaneous slow recovery of diabetes induced in a low-dose STZ mice model. We then investigated the underlying mechanisms and analyzed the cell source for the recovery of beta-cells. We showed here that postnatal day 7 (P7) female mice treated with 50 mg/kg STZ underwent the destruction of a large proportion of beta-cells and developed hyperglycemia. The blood glucose increased gradually and reached a peak level at 500 mg/dl on day 35-50. This was followed by a spontaneous regeneration of beta-cells. A reversal of non-fasting blood glucose to the control value was observed within 150 days. However, the mice still showed impaired glucose tolerance on day 150 and day 220, although a significant improvement was observed on day 150. Quantification of the beta-cell mass revealed that the beta-cell mass increased significantly between day 100 and day 150. On day 150 and day 220, the beta-cell mass was approximately 23% and 48.5% of the control, respectively. Of the insulin-positive cells, 10% turned out to be PCNA-positive proliferating cells. Our results demonstrated that, beta-cell duplication is one of the cell sources for beta-cell regeneration. (C) 2012 Elsevier Inc. All rights reserved.