Division of Endocrinology and Diabetes, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Diabetes. 2013 May;62(5):1634-45. doi: 10.2337/db12-0848. Epub 2013 Jan 24.
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.
成体β细胞祖细胞的存在仍然是糖尿病研究中最具争议的发育生物学课题。据报道，通过导管结扎诱导成年小鼠胰腺损伤，可以激活β细胞祖细胞，并且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细胞质量增加一倍。在这里，我们证明胰腺导管结扎（PDL）不会激活祖细胞来促进β细胞质量的扩张。相反，PDL 会刺激胰腺的大量损伤，从而改变胰腺的组成，因此通过传统的形态计量学方法对β细胞含量进行准确测量变得复杂，因为这些方法只是对胰腺进行表面采样。为了克服这种潜在的偏差，我们从整个胰腺中定量β细胞，并观察到 PDL 诱导的损伤不会使β细胞质量和胰岛素含量发生变化。使用连续给予胸苷类似物、大鼠胰岛素 2 启动子驱动的 cre-lox 和低频普遍 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，β细胞不会在受伤的成年小鼠胰腺中产生。
