Department of Veterans Affairs Medical Center, Louisville, KY, USA.
Islets. 2009 Jul-Aug;1(1):50-4. doi: 10.4161/isl.1.1.8936.
Despite the source or mechanism of origin of islets of Langerhans or islet β-cells, all suffer significant cell loss from ischemia after isolation, thereby reducing the surviving islet mass available for study or transplantation. Methods to reduce beta cell death after islet isolation and transplantation must be developed if islet transplantation is to become an accepted treatment for diabetes. In order to enhance intracellular oxygen delivery and utilization, islets were transfected with a plasmid encoding cytoglobin, an intracellular oxygen binding protein. Oxygen consumption, insulin secretion, and the degree of central islet necrosis were measured in untreated and transfected islets to test the effects of cytoglobin on islet survival and function in vitro. The presence of cytoglobin reduced islet cell loss by reducing hypoxia related central islet necrosis and increased insulin secretion as compared with untreated islets. Cytoglobin treated islets maintained a normal rate of oxygen consumption, while untreated islets increased the rate of oxygen consumption caused by a shift to anaerobic metabolism and increased reactive oxygen specie synthesis. The induction of cytoglobin in islets may reduce cell loss from chronic hypoxia and may be a useful adjunct to islet transplantation.
尽管胰岛或胰岛 β 细胞的来源或机制不同，但在分离后所有细胞都会因缺血而遭受严重的细胞死亡，从而减少了可用于研究或移植的存活胰岛质量。如果胰岛移植要成为糖尿病的一种公认治疗方法，就必须开发出在胰岛分离和移植后减少 β 细胞死亡的方法。为了增强细胞内氧气的输送和利用，将编码细胞结合珠蛋白的质粒转染到胰岛中，细胞结合珠蛋白是一种细胞内氧结合蛋白。在未处理和转染的胰岛中测量了氧消耗、胰岛素分泌和胰岛中心坏死的程度，以测试细胞结合珠蛋白对胰岛体外存活和功能的影响。与未处理的胰岛相比，细胞结合珠蛋白的存在减少了缺氧相关的胰岛中心坏死，从而减少了胰岛细胞的丢失，并增加了胰岛素的分泌。细胞结合珠蛋白处理的胰岛保持正常的耗氧量，而未处理的胰岛则通过转向无氧代谢和增加活性氧物质的合成而增加了耗氧量。在胰岛中诱导细胞结合珠蛋白可能会减少慢性缺氧引起的细胞丢失，并且可能是胰岛移植的有用辅助手段。
