Regeneration of pancreatic non-β endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin.
Regeneration of pancreatic non-β endocrine cells in adult mice following a single diabetes-inducing dose of streptozotocin.
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DOI：
10.1371/journal.pone.0036675
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Zhang Y;Zhang Y;Bone RN;Cui W;Peng JB;Siegal GP;Wang H;Wu H
胰岛中的非β内分泌细胞在血糖稳态调节中起着与胰岛素分泌β细胞相对应的重要作用。虽然对成人β细胞再生的理解已经取得了重大进展，但对非β内分泌细胞如产生胰高血糖素的α细胞和产生生长抑素的δ细胞的再生知之甚少。先前的研究已经注意到糖尿病患者和动物模型中α细胞组成的增加。因此，我们的假设是，成人中的非β细胞如α细胞和δ细胞可以再生，并且在糖尿病条件下再生加速。为了验证这一假设，我们详细研究了链脲佐菌素（STZ）诱导的糖尿病小鼠模型中的胰岛细胞组成。我们的数据显示，在STZ介导的β细胞破坏后，每个胰岛中的α细胞数量增加，在第6天达到峰值，约为正常胰岛的3倍。此外，我们发现STZ治疗后第6天δ细胞数量增加一倍。这些数据表明，在小鼠中单次糖尿病诱导剂量的STZ后，α和δ细胞再生迅速发生。使用体内BrdU标记技术，我们证明α-和δ-细胞再生涉及细胞增殖。用增殖细胞标记物Ki 67对胰岛进行共染色显示α-和δ-细胞可以复制，表明自我复制在其再生中发挥了作用。此外，在STZ处理后检测到Pdx 1 +/胰岛素−细胞，表明内分泌祖细胞参与了这些非β细胞的再生。这通过STZ处理后Pdx 1 +/胰高血糖素+细胞和Pdx 1 +/生长抑素+细胞的检测进一步证实。总之，我们的研究表明，成年α-和δ-细胞可以再生，自我复制和内分泌前体细胞的再生都参与了它们的再生。
The non-β endocrine cells in pancreatic islets play an essential counterpart and regulatory role to the insulin-producing β-cells in the regulation of blood-glucose homeostasis. While significant progress has been made towards the understanding of β-cell regeneration in adults, very little is known about the regeneration of the non-β endocrine cells such as glucagon-producing α-cells and somatostatin producing δ-cells. Previous studies have noted the increase of α-cell composition in diabetes patients and in animal models. It is thus our hypothesis that non-β-cells such as α-cells and δ-cells in adults can regenerate, and that the regeneration accelerates in diabetic conditions. To test this hypothesis, we examined islet cell composition in a streptozotocin (STZ)-induced diabetes mouse model in detail. Our data showed the number of α-cells in each islet increased following STZ-mediated β-cell destruction, peaked at Day 6, which was about 3 times that of normal islets. In addition, we found δ-cell numbers doubled by Day 6 following STZ treatment. These data suggest α- and δ-cell regeneration occurred rapidly following a single diabetes-inducing dose of STZ in mice. Using in vivo BrdU labeling techniques, we demonstrated α- and δ-cell regeneration involved cell proliferation. Co-staining of the islets with the proliferating cell marker Ki67 showed α- and δ-cells could replicate, suggesting self-duplication played a role in their regeneration. Furthermore, Pdx1+/Insulin− cells were detected following STZ treatment, indicating the involvement of endocrine progenitor cells in the regeneration of these non-β cells. This is further confirmed by the detection of Pdx1+/glucagon+ cells and Pdx1+/somatostatin+ cells following STZ treatment. Taken together, our study demonstrated adult α- and δ-cells could regenerate, and both self-duplication and regeneration from endocrine precursor cells were involved in their regeneration.
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