Davalli A M, Ogawa Y, Ricordi C, Scharp D W, Bonner-Weir S, Weir G C
Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
Transplantation. 1995 Mar 27;59(6):817-20.
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.
链脲佐菌素诱导的糖尿病裸鼠（血糖493±14mg/dl）在肾被膜下接受2000个人胰岛当量（IE）的等分试样，然后随访长达30天，测量血糖浓度和体重。植入前胰岛等分试样的特征包括通过免疫染色切片的点计数形态计量学评估内分泌β细胞和非β细胞质量。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±11mg/dl，30天时进一步降至70±3mg/dl。尽管血糖水平逐渐改善，但胰岛移植物的β细胞质量随时间显著下降，从移植时的2.63±0.2mg分别降至移植后15天和30天的1.16±0.1mg和0.86±0.1mg。相比之下，内分泌非β细胞质量从植入前到植入后30天保持稳定。因此，内分泌非β细胞/β细胞比率从移植时的14%分别增加到移植后15天和30天的35%和37%。在移植后15天和30天收获的移植物中，移植β细胞的复制率相似，注射溴脱氧尿苷（BrdU）6小时后，BrdU掺入阳性的β细胞百分比约为0.1%。这些数据表明，胰岛移植后β细胞质量立即发生重要下降——最显著的下降发生在最初15天，即使在血管再通后仍持续存在。然而，内分泌非β细胞质量保持稳定，表明植入的非β细胞比β细胞更不容易死亡。人胰岛移植物的非β/β细胞比率会随时间增加这一发现，引发了关于这种胰岛结构变化是否会影响功能的问题。
