Beta Cell Biology Unit, San Raffaele Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Milan, Italy.
Islets. 2009 Jul-Aug;1(1):42-9. doi: 10.4161/isl.1.1.8881.
In this study we examined the effect of rapamycin (RAPA), a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function in vivo.
Diabetic C57BL/6 or BALB/C recipient mice were transplanted with 350 syngeneic islets through the portal vein (PV-Tx; C57BL/6 n = 60; BALB/C n = 22) and treated with once-daily oral RAPA (1 mg/kg) or vehicle. No differences in post-transplant blood glucose concentrations and glucose tolerance were observed between RAPA- and vehicle-treated mice. The impact of RAPA on human islet engraftment was assessed in 10 patients with type 1 diabetes treated with : 0.1 mg/kg/day rapamycin before islet transplantation. Compared to non pre-treated islet transplant recipients (n = 12), RAPA pre-treated patients had increased blood RAPA concentrations (p = 0.006) and fasting C-peptide concentrations (p = 0.005) in the two weeks post-transplant. RAPA pre-treatment was associated with a reduction in chemokines CCL2 and CCL3 concentrations pre-transplant (p < 0.01), and a dampened chemokine response (p = 0.005) post-transplant. Concordantly, in vitro RAPA inhibited the secretion of CCL2 and CCL3 by monocytes.
Rapamycin does not adversely affect intrahepatic islet engraftment in the mouse, and potentially improves islet engraftment in humans by an anti-inflammatory mechanism.
本研究旨在探讨雷帕霉素（RAPA）对体内胰岛移植的胰岛植入和功能的影响。雷帕霉素是临床胰岛移植免疫抑制方案的关键组成部分。
糖尿病 C57BL/6 或 BALB/C 受体小鼠通过门静脉（PV-Tx；C57BL/6 n = 60；BALB/C n = 22）移植 350 个同种异体胰岛，并接受每日一次口服 RAPA（1mg/kg）或载体治疗。RAPA 和载体处理的小鼠在移植后血糖浓度和葡萄糖耐量方面没有差异。在接受 1 型糖尿病治疗的 10 例患者中评估了 RAPA 对人胰岛植入的影响：在胰岛移植前每天用 0.1mg/kg 雷帕霉素治疗。与未经预处理的胰岛移植受者（n = 12）相比，RAPA 预处理患者在移植后两周内血 RAPA 浓度（p = 0.006）和空腹 C 肽浓度（p = 0.005）升高。RAPA 预处理与移植前趋化因子 CCL2 和 CCL3 浓度降低（p < 0.01）以及移植后趋化因子反应减弱（p = 0.005）相关。相应地，体外 RAPA 抑制了单核细胞分泌 CCL2 和 CCL3。
雷帕霉素在小鼠体内不会对肝内胰岛植入产生不利影响，并可能通过抗炎机制改善人类胰岛的植入。
