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维持血糖正常所需的胰岛最小数量及其移植到糖尿病小鼠后免疫原性的降低。

Minimum number of islets required to maintain euglycemia and their reduced immunogenicity after transplantation into diabetic mice.

作者信息

Ohzato H, Porter J, Monaco A P, Montana E, Maki T

机构信息

Division of Organ Transplantation, New England Deaconess Hospital, Boston, MA 02215.

出版信息

Transplantation. 1993 Aug;56(2):270-4. doi: 10.1097/00007890-199308000-00003.

DOI:10.1097/00007890-199308000-00003
PMID:8356579
Abstract

In streptozocin (SZ)-induced diabetic mice, 200 islets, but not 50 islets, consistently restore euglycemia within 1 week of transplantation. To determine the minimum number of islets sufficient to maintain euglycemia in a diabetic mouse, we first transplanted 50 and 150 syngeneic islets simultaneously into the right (RK) and left kidney (LK), respectively, and then removed the LK 1 week post-transplantation. The remaining 50 islets maintained euglycemia in 8 of 11 mice with normal intravenous glucose tolerance tests (IVGTT). Protection of 50 islets for at least 7 days was necessary because removal of the 150 islets at 5 or 3 days resulted in a much lower incidence of persistent euglycemia. Similarly, 25 islets were capable of maintaining euglycemia in 2 of 9 mice once hyperglycemia was reversed by split-transplantation of 25 (RK) and 175 (LK) islets. To examine if 50-islet allografts survive longer than 200-islet allografts, we split-transplanted 50 DBA/2 islets in the RK and 150 islets of either B6 (syngeneic), DBA/2 (allogeneic), or C3H/He (third party allogeneic) mouse origin in the LK in 3 groups of diabetic C57BL/6 (B6) mice. The survival of 50 DBA/2 islets in each group after removal of the LK on day 7 was compared to that of 200 DBA/2 islets in control B6 mice. Maximum prolongation of allograft survival was obtained with 50 DBA/2 islets that were split-transplanted with syngeneic B6 islets. These results clearly demonstrate that 50 islets are sufficient to maintain normal glucose tolerance once euglycemia is induced by transplantation of a larger number (i.e., 200) of islets and that 50 islet allografts are much less immunogenic than 200-islet allografts.

摘要

在链脲佐菌素(SZ)诱导的糖尿病小鼠中,200个胰岛移植后能在1周内持续恢复正常血糖水平,而50个胰岛则不能。为了确定维持糖尿病小鼠正常血糖水平所需的最少胰岛数量,我们首先将50个和150个同基因胰岛分别同时移植到右侧肾脏(RK)和左侧肾脏(LK),然后在移植后1周切除LK。在11只静脉葡萄糖耐量试验(IVGTT)正常的小鼠中,剩余的50个胰岛使8只小鼠维持了正常血糖水平。保护50个胰岛至少7天是必要的,因为在5天或3天切除150个胰岛后,持续正常血糖水平的发生率要低得多。同样,一旦通过分别移植25个(RK)和175个(LK)胰岛逆转高血糖后,25个胰岛能够使9只小鼠中的2只维持正常血糖水平。为了研究50个胰岛的同种异体移植是否比200个胰岛的同种异体移植存活时间更长,我们将3组糖尿病C57BL/6(B6)小鼠的RK分别移植50个DBA/2胰岛,LK分别移植150个来自B6(同基因)、DBA/2(同种异体)或C3H/He(第三方同种异体)小鼠的胰岛。在第7天切除LK后,比较每组中50个DBA/2胰岛的存活情况与对照B6小鼠中200个DBA/2胰岛的存活情况。与同基因B6胰岛一起进行分割移植的50个DBA/2胰岛使同种异体移植存活时间得到了最大程度的延长。这些结果清楚地表明,一旦通过移植大量(即200个)胰岛诱导出正常血糖水平,50个胰岛就足以维持正常的葡萄糖耐量,并且50个胰岛的同种异体移植比200个胰岛的同种异体移植免疫原性要低得多。

相似文献

1
Minimum number of islets required to maintain euglycemia and their reduced immunogenicity after transplantation into diabetic mice.维持血糖正常所需的胰岛最小数量及其移植到糖尿病小鼠后免疫原性的降低。
Transplantation. 1993 Aug;56(2):270-4. doi: 10.1097/00007890-199308000-00003.
2
Fifty islets maintain euglycemia and survive longer than 200 islets in allogeneic and xenogeneic diabetic hosts.在同种异体和异种糖尿病宿主中,50个胰岛可维持血糖正常,且比200个胰岛存活时间更长。
Transplant Proc. 1993 Feb;25(1 Pt 2):953-4.
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Triptolide prolonged allogeneic islet graft survival in chemically induced and spontaneously diabetic mice without impairment of islet function.雷公藤内酯醇可延长化学诱导和自发性糖尿病小鼠同种异体胰岛移植物的存活时间,而不损害胰岛功能。
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Multiple donor allotransplantation. A new approach to pancreatic islet transplantation.多供体同种异体移植。胰岛移植的一种新方法。
Transplantation. 1988 Jun;45(6):1008-12.
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Leptin administration enhances islet transplant performance in diabetic mice.瘦素给药增强糖尿病小鼠胰岛移植的效果。
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引用本文的文献

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Evaluation of low doses BPA-induced perturbation of glycemia by toxicogenomics points to a primary role of pancreatic islets and to the mechanism of toxicity.通过毒理基因组学评估低剂量双酚A诱导的血糖紊乱,揭示了胰岛的主要作用及其毒性机制。
Cell Death Dis. 2015 Oct 29;6(10):e1959. doi: 10.1038/cddis.2015.319.
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Beneficial effect of insulin treatment on islet transplantation outcomes in Akita mice.胰岛素治疗对秋田小鼠胰岛移植结局的有益作用。
PLoS One. 2014 Apr 17;9(4):e95451. doi: 10.1371/journal.pone.0095451. eCollection 2014.
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Transplanted beta cell response to increased metabolic demand. Changes in beta cell replication and mass.
移植的β细胞对代谢需求增加的反应。β细胞复制和质量的变化。
J Clin Invest. 1994 Apr;93(4):1577-82. doi: 10.1172/JCI117137.