• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Islets >AEB071 (sotrastaurin) does not exhibit toxic effects on human islets in vitro nor after transplantation into immunodeficient mice
【24h】

AEB071 (sotrastaurin) does not exhibit toxic effects on human islets in vitro nor after transplantation into immunodeficient mice

机译：AEB071（sotrastaurin）在体外或移植到免疫缺陷小鼠后对人胰岛均无毒性作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

AEB071 (AEB, sotrastaurin), a specific inhibitor of protein kinase C, reduces T lymphocyte activation and cytokine release. AEB delays islet allograft rejection in rats and prevents rejection when combined with cyclosporine. Since many immunosuppressive agents have toxic effects on the function of transplanted islets, we investigated whether this was also the case with AEB. Human islets were transplanted into Rag-knockout mice randomly assigned to vehicle control, AEB or sirolimus treatment groups. Non-fasting blood glucose levels, body weight and glucose tolerance was measured in recipients. In a separate experiment, human islets were cultured in the presence of AEB and assayed for glucose dependent insulin secretion and level of β-cell apoptosis. Eighty-six percent of the AEB-treated recipients achieved normoglycemia following transplant (compared with none in sirolimus-treated group, p < 0.05). AEB-treated recipients exhibited similar glucose homeostasis as vehicle-treated controls, which was better than in sirolimus-treated recipients. Human islets cultured with AEB showed similar rates of β-cell apoptosis (p = 0.98 by one-way ANOVA) and glucose stimulated insulin secretion (p = 0.15) as those cultured with vehicle. These results suggest that AEB is not associated with toxic effects on islet engraftment or function. AEB appears to be an appropriate immunosuppressive candidate for clinical trials in islet transplantation.
机译：AEB071（AEB，sotrastaurin），一种蛋白激酶C的特异性抑制剂，可降低T淋巴细胞活化和细胞因子释放。 AEB可延缓大鼠胰岛同种异体移植的排斥反应，并与环孢素联合使用时可防止排斥反应。由于许多免疫抑制剂对移植的胰岛功能均具有毒性作用，因此我们调查了AEB是否也是这种情况。将人类胰岛移植到随机分为媒介物对照，AEB或西罗莫司治疗组的Rag敲除小鼠中。在接受者中测量非空腹血糖水平，体重和葡萄糖耐量。在一个单独的实验中，在AEB的存在下培养人胰岛，并测定葡萄糖依赖性胰岛素分泌和β细胞凋亡水平。接受AEB治疗的受试者中有86％在移植后达到了正常血糖水平（与西罗莫司治疗组相比没有，p <0.05）。 AEB治疗的受试者表现出与溶媒治疗的对照组相似的葡萄糖稳态，这优于西罗莫司治疗的受试者。用AEB培养的人胰岛显示出与用媒介物培养时相似的β细胞凋亡率（单向ANOVA，p = 0.98）和葡萄糖刺激的胰岛素分泌（p = 0.15）。这些结果表明，AEB与胰岛植入或功能的毒性作用无关。 AEB似乎是胰岛移植临床试验中合适的免疫抑制候选物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号