A selective decrease in the beta cell mass of human islets transplanted into diabetic nude mice.
A selective decrease in the beta cell mass of human islets transplanted into diabetic nude mice.
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DOI：
10.1097/00007890-199503000-00003
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发表时间：
1995-03
期刊：
影响因子：
6.2
通讯作者：
A. Davalli;Y. Ogawa;C. Ricordi;D. Scharp;S. Bonner-Weir;G. Weir
中科院分区：
文献类型：
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作者：
A. Davalli;Y. Ogawa;C. Ricordi;D. Scharp;S. Bonner-Weir;G. Weir
链脲佐菌素诱导的糖尿病裸鼠（血糖 493 +/- 14 mg/dl）在肾囊下接受 2000 个人类胰岛当量 (IE) 等分试样，然后进行长达 30 天的随访，测量血糖浓度和体重。植入前胰岛等分试样的表征包括内分泌β细胞和非β细胞质量的评估，通过免疫染色切片的点计数形态测量来估计。胰岛移植后，血糖水平迅速下降，体重逐渐增加；移植后 15 天，平均血糖水平为 102 +/- 11 mg/dl，并在 30 天时进一步降至 70 +/- 3 mg/dl。尽管葡萄糖水平逐渐改善，但胰岛移植物的β细胞质量随着时间的推移显着下降，从移植时的2.63 +/- 0.2 mg分别降至移植后15天和30天的1.16 +/- 0.1和0.86 +/- 0.1 mg。相反，从植入前到植入后30天，内分泌非β细胞团保持稳定。因此，内分泌非β细胞/β细胞比率从移植时的14%分别增加至移植后15天和30天的35%和37%。在 15 天和 30 天收获的移植物中，移植的 β 细胞的复制率相似，注射 BrdU 后 6 小时，溴-2'脱氧尿苷 (BrdU) 掺入呈阳性的 β 细胞百分比约为 0.1%。这些数据表明，胰岛移植后，β 细胞量立即发生显着减少，最显着的减少发生在前 15 天，甚至在血运重建后仍持续存在。然而，内分泌非β细胞群保持稳定，表明移植的非β细胞比β细胞更不可能死亡。人类胰岛移植物的非β/β细胞比例会随着时间的推移而增加，这一发现提出了这样的问题：胰岛结构的这种变化是否会对功能产生影响。
Streptozocin-induced diabetic nude mice (blood glucose 493 +/- 14 mg/dl) received aliquots of 2000 human islet equivalents (IE) under the kidney capsule and were then followed for up to 30 days with measurement of blood glucose concentration and body weight. Characterization of islet aliquots before the implantation included the assessment of the endocrine beta cell and nonbeta cell mass, estimated by point counting morphometry of immunostained sections. Islet transplantation was followed by a rapid decrease in blood glucose levels and by a progressive increase in body weight; 15 days after transplantation mean glycemic levels were 102 +/- 11 mg/dl and further decreased to 70 +/- 3 mg/dl at 30 days. Despite the progressive improvement in the glucose levels, the beta cell mass of the islet grafts significantly decreased over time from 2.63 +/- 0.2 mg, at the time of transplantation, to 1.16 +/- 0.1 and 0.86 +/- 0.1 mg 15 and 30 days, respectively, after transplantation. In contrast, the endocrine nonbeta cell mass remained stable from before the implantation to 30 days after. Therefore, the endocrine nonbeta cell/beta cell ratio increased from 14% at the time of transplantation, to 35% and 37%, 15 and 30 days, respectively, after transplantation. The rate of replication of the transplanted beta cells was similar in the grafts harvested at 15 and 30 days, with the percentage of beta cells positive for bromo-2' deoxyuridine (BrdU) incorporation being in the range of approximately 0.1% 6 hr after the BrdU injection. These data demonstrate that an important decrease in beta cell mass takes place immediately after islet transplantation--the most dramatic decrease occurring in the first 15 days and persisting even after revascularization has occurred. However, endocrine nonbeta cell mass remained stable indicating that engrafted nonbeta cells are less likely to die than beta cells. The finding that the nonbeta/beta cell ratio of a human islet graft can increase over time, raises questions about whether such a change in islet structure could have an influence upon function.