Merino J F, Nacher V, Raurell M, Aranda O, Soler J, Montanya E
Laboratory of Diabetes and Experimental Endocrinology, C.S.U.B.-Hospital de Bellvitge, University of Barcelona, Spain.
Diabetologia. 1997 Sep;40(9):1004-10. doi: 10.1007/s001250050781.
Insulin treatment may improve the outcome of islet transplantation. To determine the effects of insulin treatment on transplanted islets, 4 groups of streptozotocin-diabetic C57BL/6 mice were transplanted with 100 islets, an insufficient beta-cell mass to restore normoglycaemia. Groups 1 (n = 12) and 2 (n = 12), were kept normoglycaemic with insulin treatment from day 10 before transplantation to day 14 after transplantation; groups 3 (n = 12) and 4 (n = 18), were not treated with insulin. Grafts were harvested 14 (groups 1 and 3) or 60 (groups 2 and 4) days after transplantation and beta-cell mass and replication were measured. When insulin was discontinued all mice maintained normoglycaemia; in contrast, non-insulin-treated groups remained hyperglycaemic throughout the study. Fourteen days after transplantation the beta-cell mass was reduced both in group 1 (0.09 +/- 0.01 mg) and group 3 (0.14 +/- 0.02 mg) compared to the initially transplanted mass (0.22 +/- 0.02 mg, p < 0.01); beta-cell replication and area did not change in group 1, but were increased in group 3. Insulin content, expressed as a function of beta-cell mass, was maintained in group 1 grafts (12.5 +/- 2.0 micrograms/mg), but was severely reduced in group 3 (1.0 +/- 0.2 micrograms/mg) compared to non-transplanted islets (20.4 +/- 3.3 micrograms/mg). In group 2, beta-cell mass increased when insulin was discontinued; 60 days after transplantation beta-cell mass was similar to the initially transplanted mass (0.23 +/- 0.04 mg), glucose levels after an intraperitoneal glucose challenge were normal, and insulin content was preserved (19.6 +/- 2.7 micrograms/mg). In contrast, beta-cell mass was progressively reduced in group 4 (0.08 +/- 0.02 mg, p < 0.001). In summary, insulin treatment reduced the beta-cell mass needed to achieve normoglycaemia in islet transplantation. Islets transplanted to insulin-treated mice showed better beta-cell function, preserved insulin content, and were able to increase their beta-cell mass to meet an increased functional demand.
胰岛素治疗可能会改善胰岛移植的结果。为了确定胰岛素治疗对移植胰岛的影响，将4组链脲佐菌素诱导的糖尿病C57BL/6小鼠移植100个胰岛，这一β细胞量不足以恢复正常血糖水平。第1组（n = 12）和第2组（n = 12），从移植前10天至移植后14天接受胰岛素治疗以维持正常血糖水平；第3组（n = 12）和第4组（n = 18），未接受胰岛素治疗。在移植后14天（第1组和第3组）或60天（第2组和第4组）采集移植物，并测量β细胞量和复制情况。当停用胰岛素后，所有小鼠均维持正常血糖水平；相比之下，未接受胰岛素治疗的组在整个研究过程中均保持高血糖状态。移植后14天，第1组（0.09±0.01mg）和第3组（0.14±0.02mg）的β细胞量均低于最初移植的量（0.22±0.02mg，p<0.01）；第1组的β细胞复制和面积未发生变化，但第3组有所增加。以β细胞量为函数表示的胰岛素含量，在第1组移植物中得以维持（12.5±2.0μg/mg），但与未移植的胰岛（20.4±3.3μg/mg）相比，第3组严重降低（1.0±0.2μg/mg）。在第2组中，停用胰岛素后β细胞量增加；移植后60天，β细胞量与最初移植的量相似（0.23±0.04mg），腹腔注射葡萄糖激发后的血糖水平正常，且胰岛素含量得以保留（19.6±2.7μg/mg）。相比之下，第4组的β细胞量逐渐减少（0.08±0.02mg，p<0.001）。总之，胰岛素治疗减少了胰岛移植中实现正常血糖水平所需的β细胞量。移植到接受胰岛素治疗小鼠体内的胰岛表现出更好的β细胞功能、保留的胰岛素含量，并且能够增加其β细胞量以满足增加的功能需求。
