Clinical Islet Transplant Program, Department of Surgery, University of Alberta, Edmonton, AB, Canada.
Transpl Int. 2010 Mar 1;23(3):259-65. doi: 10.1111/j.1432-2277.2009.00984.x. Epub 2009 Oct 12.
The culture of human islets is associated with approximately 10-20% islet loss, occasionally preventing transplantation. Preconditioning of the islets to improve postculture yields would be of immediate benefit, with the potential to increase both the number of transplanted patients and their metabolic reserve. In this study, the effect of liraglutide, a long-acting human glucagon-like peptide 1 analogue, on cultured human islets was examined. Culture with liraglutide (1 micromol/l) was associated with a preservation of islet mass (significantly more islets at 24 and 48 h, compared to control; P < or = 0.05 at 24 and 48 h) and with the presence of larger islets (P < or = 0.05 at 48 h). These observations were supported by reduced apoptosis rates after 24 h of treatment. We also demonstrated that human islet engraftment is improved in C57Bl/6-RAG(-/-) mice treated with liraglutide 200 microg/kg sc twice daily (P < or = 0.05), suggesting that liraglutide should be continued after transplantation. Overall, these data demonstrate the beneficial effect of liraglutide on cultured human islets, preserving islet mass. They support the design of clinical studies looking at the effect of liraglutide in clinical islet transplantation.
人胰岛的培养与大约 10-20%的胰岛损失有关,偶尔会妨碍移植。对胰岛进行预处理以提高培养后产量将立即带来益处,有可能增加接受移植的患者数量及其代谢储备。在这项研究中,研究了长效人胰高血糖素样肽 1 类似物利拉鲁肽对培养的人胰岛的作用。用利拉鲁肽(1 微摩尔/升)培养与胰岛质量的保存有关(与对照组相比,在 24 小时和 48 小时时的胰岛数量明显更多;在 24 小时和 48 小时时均 P<0.05),并且存在更大的胰岛(在 48 小时时 P<0.05)。这些观察结果得到了处理 24 小时后细胞凋亡率降低的支持。我们还证明,用利拉鲁肽(每天两次皮下注射 200 微克/千克)治疗 C57Bl/6-RAG(-/-) 小鼠可改善人胰岛的移植,表明在移植后应继续使用利拉鲁肽。总体而言,这些数据表明利拉鲁肽对培养的人胰岛具有有益作用,可保存胰岛质量。它们支持设计临床研究,以观察利拉鲁肽在临床胰岛移植中的作用。