Increased β-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse
Increased β-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse
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DOI：
10.2337/diabetes.48.5.989
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发表时间：
1999-05-01
期刊：
影响因子：
7.7
通讯作者：
Polonsky, KS
中科院分区：
文献类型：
--
作者：
Sreenan, S;Pick, AJ;Polonsky, KS
为了确定NOD小鼠中β细胞质量和功能的丧失是逐渐发生的，在胰岛炎发作后开始，还是突然发生的，就在明显糖尿病发作前，在8-9、13和18周龄的NOD和对照NOD/Scid小鼠中测量来自灌注胰腺的β细胞质量和β细胞增殖速率以及胰岛素分泌反应。在NOD小鼠中，分别有11%和70%在13和18周龄时患有糖尿病（空腹血糖>8.3 mmol/l）。8周龄NOD小鼠的β细胞质量是对照小鼠的69（P > 0.05），但5-溴-2-脱氧尿苷摄取率更高，表明对持续的自身免疫性β细胞破坏的代偿性增殖反应。尽管β细胞增殖率增加，在13周龄的非糖尿病NOD小鼠中，β-细胞质量显著减少了42%，在18周龄的糖尿病NOD小鼠中，β-细胞质量显著减少了73%。胰岛素分泌反应葡萄糖和精氨酸表现出类似的幅度减少。在18周龄的糖尿病NOD小鼠中，胰岛素分泌减少的程度大于β细胞质量，这表明除了质量减少之外还存在β细胞功能障碍。这些结果表明，在NOD小鼠中，胰岛炎发作后不久β细胞就开始破坏。尽管存在代偿性β细胞增殖反应，但β细胞质量逐渐福尔斯下降，并且在13周时显著降低，尽管血糖浓度正常。当残留的β细胞质量占对照水平的30%时，可能存在糖尿病。
To determine whether loss of beta-cell mass and function in the NOD mouse occurs gradually, beginning after the onset of insulitis, or abruptly, just before the onset of overt diabetes, beta-cell mass and rates of beta-cell proliferation and insulin secretory responses from the perfused pancreas were measured in NOD and control NOD/Scid mice at 8-9, 13, and 18 weeks of age. Of the NOD mice, 11 and 70% had diabetes (fasting blood glucose >8.3 mmol/l) at 13 and 18 weeks of age, respectively. beta-cell mass in 8-week-old NOD mice was 69% of control mice (P > 0.05), but the rate of 5-bromo-2-deoxyuridine uptake was greater, suggesting a compensatory proliferative response to ongoing autoimmune beta-cell destruction, Despite an increase in the rate of beta-cell proliferation, beta-cell mass was significantly reduced by 42% in 13-week-old nondiabetic NOD mice and by 73% in 18-week-old diabetic NOD mice. Insulin secretory responses to glucose and arginine demonstrated reductions of similar magnitude. In 18-week-old diabetic NOD mice, insulin secretion was reduced to a greater degree than beta-cell mass, suggesting the presence of beta-cell dysfunction in addition to reduced mass. These results suggest that in the NOD mouse, beta-cell destruction begins soon after the onset of insulitis. Despite a compensatory beta-cell proliferative response, beta-cell mass progressively falls and is significantly reduced by 13 weeks despite normal blood glucose concentrations. Diabetes may be present when residual beta-cell mass represents 30% of control levels.