Vulnerability of islets in the immediate posttransplantation period - Dynamic changes in structure and function
Vulnerability of islets in the immediate posttransplantation period - Dynamic changes in structure and function
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DOI：
10.2337/diabetes.45.9.1161
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发表时间：
1996-09-01
期刊：
影响因子：
7.7
通讯作者：
Weir, GC
中科院分区：
文献类型：
--
作者：
Davalli, AM;Scaglia, L;Weir, GC
为了进一步了解胰岛在移植后即刻的易损性，将400个同基因胰岛移植到B6AF1小鼠的肾被膜下，使用三组受体：正常小鼠(正常组)、链脲佐菌素(STZ)糖尿病组(糖尿病组)和STZ糖尿病用胰岛素颗粒维持低血糖或正常血糖组(糖尿病正常组)。3组移植后14d血糖均正常，而糖尿病组和糖尿病正常组移植后血糖水平分别高于和低于正常组，移植后1、3、7、14d取材，观察形态、β细胞死亡、β细胞质量、胰岛素含量和胰岛素基因表达，各组移植胰岛在移植后第1、3天均出现明显损伤，出现凋亡核和坏死核；第3天糖尿病组β细胞死亡明显高于其他组，第14天各组均出现组织重塑，移植物形态稳定；糖尿病组移植物的实际胰岛β细胞质量最低，移植物胰岛素含量在第1天、第3天和第7天进一步下降。糖尿病组和糖尿病正常组移植物的胰岛素mRNA水平在第1天就已低于正常组，第14天仍低于正常组。结论：胰岛移植的最初几天，即使在代谢控制最好的情况下，也具有动态变化的特点，即胰岛细胞功能障碍和死亡，随后组织重塑，然后稳定植入。
To learn more about islet vulnerability in the immediate posttransplant period, 400 syngeneic islets were transplanted under the kidney capsule of B6AF1 mice, Three groups of recipients were used: normal mice (normal), streptozotocin (STZ)-diabetic (diabetic), and STZ-diabetic kept hypo- or normoglycemic with insulin pellets (diabetic-normalized). Normoglycemia was achieved in all three groups 14 days after transplantation; however, in the diabetic and diabetic-normalized groups, blood glucose levels throughout the posttransplantation period were respectively higher and lower than in the normal group, Grafts were harvested 1, 3, 7, and 14 days after transplantation and analyzed for morphology, beta-cell death, beta-cell mass, insulin content, and insulin mRNA expression, In all groups, substantial damage in islet grafts was found on days 1 and 3 with apoptotic nuclei and necrotic cores; on day 3, beta-cell death was significantly higher in the diabetic group than in the other groups, Tissue remodeling occurred in all groups with stable graft appearance on day 14; the actual beta-cell mass of the grafts was lowest in the diabetic group, Graft insulin content decreased in all groups on day 1 and feb even further on days 3 and 7. Insulin mRNA levels of grafts retrieved from both the diabetic and diabetic-normalized group were lower than those from the normal group already by day 1 and remained lower on day 14, In conclusion, the first few days of islet transplantation, even under the most advantageous circumstances of excellent metabolic control, are characterized by dynamic changes, with substantial islet cell dysfunction and death followed by tissue remodeling and then stable engraftment.