M.Eng., Montréal General Hospital C9-128, 1650 Cedar Avenue, Montréal, Québec, Canada H3G 1A4.
Endocrinology. 2010 Apr;151(4):1462-72. doi: 10.1210/en.2009-1277. Epub 2010 Feb 22.
Studies of long-standing type 2 diabetes (T2D) report a deficit in beta-cell mass due to increased apoptosis, whereas neogenesis and replication are unaffected. It is unclear whether these changes are a cause or a consequence of T2D. Moreover, whereas islet morphogenetic plasticity has been demonstrated in vitro, the in situ plasticity of islets, as well as the effect of T2D on endocrine differentiation, is unknown. We compared beta-cell volume, neogenesis, replication, and apoptosis in pancreata from lean and obese (body mass index > or = 27 kg/m(2)) diabetic (5 +/- 2 yr since diagnosis) and nondiabetic cadaveric donors. We also subjected isolated islets from diabetic (3 +/- 1 yr since diagnosis) and nondiabetic donors to an established in vitro model of islet plasticity. Differences in beta-cell volume between diabetic and nondiabetic donors were consistently less pronounced than those reported in long-standing T2D. A compensatory increase in beta-cell neogenesis appeared to mediate this effect. Studies of induced plasticity indicated that islets from diabetic donors were capable of epithelial dedifferentiation but did not demonstrate regenerative potential, as was seen in islets from nondiabetic donors. This deficiency was associated with the overexpression of Notch signaling molecules and a decreased neurogenin-3(+) cell frequency. One interpretation of these results would be that decreased beta-cell volume is a consequence, not a cause, of T2D, mediated by increased apoptosis and attenuated beta-cell (re)generation. However, other explanations are also possible. It remains to be seen whether the morphogenetic plasticity of human islets, deficient in vitro in islets from diabetic donors, is a component of normal beta-cell mass dynamics.
对长期存在的 2 型糖尿病（T2D）的研究报告称，β细胞质量由于细胞凋亡的增加而减少，而新生和复制不受影响。目前尚不清楚这些变化是 T2D 的原因还是结果。此外，虽然已经在体外证明了胰岛的形态发生可塑性，但胰岛的原位可塑性以及 T2D 对内分泌分化的影响尚不清楚。我们比较了瘦（体重指数≥27 kg/m2）和肥胖（诊断后 5±2 年）糖尿病和非糖尿病尸体供体的胰腺中的β细胞体积、新生、复制和凋亡。我们还将来自糖尿病（诊断后 3±1 年）和非糖尿病供体的分离胰岛置于已建立的胰岛可塑性体外模型中。糖尿病和非糖尿病供体之间的β细胞体积差异始终比长期 T2D 报告的差异小。β细胞新生的代偿性增加似乎介导了这种效应。诱导可塑性研究表明，糖尿病供体的胰岛能够进行上皮去分化，但没有显示出再生潜力，这在非糖尿病供体的胰岛中可见。这种缺陷与 Notch 信号分子的过度表达和神经生成素 3（+）细胞频率降低有关。对这些结果的一种解释是，β细胞体积减少是 T2D 的结果，而不是原因，由细胞凋亡增加和β细胞（再）生成减弱介导。然而，也可能存在其他解释。尚不清楚人类胰岛的形态发生可塑性是否是正常β细胞质量动态的一个组成部分，而糖尿病供体的胰岛在体外缺乏这种可塑性。
