β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.
β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.
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DOI：
10.2337/db12-0848
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发表时间：
2013-05
期刊：
影响因子：
7.7
通讯作者：
Kushner JA
中科院分区：
文献类型：
--
作者：
Rankin MM;Wilbur CJ;Rak K;Shields EJ;Granger A;Kushner JA
成体β细胞前体细胞的存在仍然是糖尿病研究中最具争议的发育生物学话题。有报道称，β细胞前体细胞可通过结扎成年小鼠胰腺而被激活，并明显以细胞自主的方式通过分化和增殖在一周内使功能性β细胞数量增加一倍。在这里，我们证明了胰管结扎术并不能激活祖细胞来促进β细胞的大量扩增。相反，PDL刺激了大量的胰腺损伤，从而改变了胰腺的成分，从而使通过传统的形态计量学方法准确测量β细胞含量变得复杂，这些方法只对胰腺进行表面采样。为了克服这种潜在的偏见，我们量化了整个胰腺的β细胞，并观察到β细胞质量和胰岛素含量在PDL诱导的损伤中完全没有变化。连续给药胸苷类似物、大鼠胰岛素2启动子驱动的cre-lox和低频无处不在的cre-lox的谱系追踪研究表明，PDL不会将祖细胞转化为β细胞谱系。因此，我们得出结论，在受损的成年小鼠胰腺中没有产生β细胞。
The existence of adult β-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that β-cell progenitors can be activated by ductal ligation–induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional β-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to β-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of β-cell content via traditional morphometry methodologies that superficially sample the pancreas. To overcome this potential bias, we quantified β-cells from the entire pancreas and observed that β-cell mass and insulin content are totally unchanged by PDL-induced injury. Lineage-tracing studies using sequential administration of thymidine analogs, rat insulin 2 promoter–driven cre-lox, and low-frequency ubiquitous cre-lox reveal that PDL does not convert progenitors to the β-cell lineage. Thus, we conclude that β-cells are not generated in injured adult mouse pancreas.
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