Recovery of pancreatic β cells in response to long-term normoglycemia after pancreas or islet transplantation in severely streptozotocin diabetic adult rats
Recovery of pancreatic β cells in response to long-term normoglycemia after pancreas or islet transplantation in severely streptozotocin diabetic adult rats
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DOI：
10.1097/00006676-200108000-00009
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发表时间：
2001-08-01
期刊：
影响因子：
2.9
通讯作者：
Lenzen, S
中科院分区：
文献类型：
--
作者：
Jörns, A;Klempnauer, J;Lenzen, S
在完善的高剂量链脲佐菌素糖尿病大鼠模型中，尚不清楚胰腺或胰岛移植后的正常血糖是否会诱导葡萄糖识别结构的表达，并刺激少数存活的胰腺β细胞的复制。因此，在全胰或离体胰岛移植肾包膜后10天和100天，用免疫细胞化学方法检测链脲佐菌素处理的主要组织相容性复合体基因Lewis大鼠的胰腺内分泌组织。在糖尿病状态下，胰腺细胞对胰岛素和葡萄糖激酶的免疫染色较弱，同时在质膜中缺乏GLUT2葡萄糖转运蛋白的免疫反应性。移植后10天，存活的β细胞的胰岛素、葡萄糖识别结构葡萄糖激酶和GLUT2葡萄糖转运蛋白的免疫染色恢复正常。移植后100天，无论是整个胰腺还是分离的胰岛，受体动物胰岛中存活的β细胞数量增加了两到三倍。再生的β细胞被其他内分泌细胞包围。β细胞数量的增加并没有伴随着胰腺导管结构新生的迹象。作者的观察结果支持这样一个概念，即通过内分泌移植物提供充足的胰岛素来严格长期维持正常血糖是β细胞恢复和葡萄糖识别结构恢复的理想前提。高剂量链脲佐菌素治疗后胰腺中β细胞的复制与终末期糖尿病β细胞的破坏。
In the well-established, high-dose streptozotocin diabetic rat model, it is unknown whether normoglycemia after pancreas or islet transplantation may induce the expression of the glucose recognition structures and stimulate the replication of the few surviving pancreatic beta cells. Therefore, the endocrine pancreatic tissue was examined immunocytochemically in streptozotocin-treated major histocompatibility complex congenic Lewis rats at 10 and 100 days after transplantation of whole pancreata or isolated islets implanted under the kidney capsule. In the diabetic state the pancreatic beta cells displayed a weak immunostaining for insulin and glucokinase together with a lack of GLUT2 glucose transporter immunoreactivity in the plasma membrane. Ten days after transplantation, the surviving beta cells had regained their normal immunostaining for Insulin and for the glucose recognition structures glucokinase and the GLUT2 glucose transporter. One hundred days after transplantation, both of whole pancreas or isolated islets, the number of surviving beta cells in islets of the pancreata of the recipient animals had increased by two- to threefold. The regenerated beta cells were surrounded by a rim of other endocrine cells. The increase in the number of beta cells was not accompanied by signs of neogenesis from ductal structures in the pancreata, The authors' observations support the concept that strict long-term maintenance of normoglycemia through adequate supply of insulin from endocrine grafts is the ideal prerequisite for beta -cell recovery and restitution of the glucose recognition structures, as well as replication of beta cells in pancreata with end-stage diabetic beta -cell destruction after high-dose streptozotocin treatment.