Glutathione ethyl ester supplementation during pancreatic islet isolation improves viability and transplant outcomes in a murine marginal islet mass model.
Glutathione ethyl ester supplementation during pancreatic islet isolation improves viability and transplant outcomes in a murine marginal islet mass model.
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DOI：
10.1371/journal.pone.0055288
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Shapiro AM
中科院分区：
文献类型：
--
作者：
do Amaral AS;Pawlick RL;Rodrigues E;Costal F;Pepper A;Galvão FH;Correa-Giannella ML;Shapiro AM
胰岛移植的成功仍然面临许多挑战，主要与胰岛分离期间和移植后早期的细胞损伤有关。胰岛分离过程中活性氧（ROS）的产生增加和抗氧化防御的消耗似乎是胰岛损伤的重要途径。在本研究中，我们评估了在小鼠边缘胰岛质量模型中，在胰岛分离期间补充谷胱甘肽乙酯（GEE）是否可以改善胰岛活力和移植结果。我们还在有或没有GEE补充的标准CMRL培养基中培养人胰岛24小时。GEE的补充降低了离体胰岛中ROS的含量，导致细胞凋亡的减少和胰岛活力的维持。移植有边缘质量的GEE处理的胰岛的小鼠在移植后变得血糖正常的百分比更高。与未处理的胰岛相比，在培养的人胰岛中补充20 mM GEE显著降低了细胞凋亡率。GEE补充能够降低细胞凋亡率和细胞内ROS含量在分离的胰岛，并可能被认为是一个潜在的干预，以提高胰岛的活力在分离过程中，并在胰岛移植前的文化维护。
The success of pancreatic islet transplantation still faces many challenges, mainly related to cell damage during islet isolation and early post-transplant. The increased generation of reactive oxygen species (ROS) during islet isolation and the consumption of antioxidant defenses appear to be an important pathway related to islet damage. In the present study we evaluated whether supplementation of glutathione-ethyl-ester (GEE) during islet isolation could improve islet viability and transplant outcomes in a murine marginal islet mass model. We also cultured human islets for 24 hours in standard CMRL media with or without GEE supplementation. Supplementation of GEE decreased the content of ROS in isolated islets, leading to a decrease in apoptosis and maintenance of islet viability. A higher percentage of mice transplanted with a marginal mass of GEE treated islets became euglycemic after transplant. The supplementation of 20 mM GEE in cultured human islets significantly reduced the apoptosis rate in comparison to untreated islets. GEE supplementation was able to decrease the apoptosis rate and intracellular content of ROS in isolated islets and might be considered a potential intervention to improve islet viability during the isolation process and maintenance in culture before islet transplantation.
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