Nishimura R, Ushiyama A, Sekiguchi S, Fujimori K, Ohuchi N, Satomi S, Goto M
Division of Advanced Surgical Science and Technology, Tohoku University, Japan.
Transplant Proc. 2013 Jun;45(5):1892-4. doi: 10.1016/j.transproceed.2013.01.047.
The subcutaneous space is an ideal site for pancreatic islet transplantation. However, one of the main obstacles is poor revascularization. Recently, glucagon-like peptide 1 (GLP-1) analogues are emerging as a new treatment option for patients with type 2 diabetes, because they have been shown to decrease β-cell apoptosis. Therefore, we hypothesized that administration of a GLP-1 analogue in the early phase may facilitate revascularization of transplanted pancreatic islets by decreasing apoptotic changes of vascular endothelial cells within and without the graft. In this study, we evaluated the effects of GLP-1 analogue liraglutide on revascularization at a subcutaneous site with the use of a highly sensitive imaging system. We combined a dorsal skinfold chamber (DSC) technique with multiphoton laser-scanning microscopy (MPLSM).
Donor pancreatic islets isolated from C57BL/6-Tg (CAG-EGFP) mice were syngeneically transplanted into a dorsal skinfold chamber mounted on recipient mice. Male C57BL/6N mouse as recipients were divided into 3 groups: control, donor islet-treated, and recipient-treated groups. In the donor islet-treated group, the pancreatic islets were cultured with liraglutide (1 μmol/L) for 24 hours. The recipient-treated mice were injected with liraglutide (100 μg/kg subcutaneously) twice daily for 8 days. The time-dependent changes of newly formed vessels surrounding the islet grafts were imaged with MPLSM on days 1, 4, and 7. To evaluate islet graft revascularization, we measured vascular volume surrounding the islet with the Volocity system.
In the first 4 days after pancreatic islet transplantation, no significant difference was detected in newly formed vessels among the 3 groups. Also, no significant difference was detected to increase rates at 7 days after transplantation.
In this study, administration of GLP-1 analogue liraglutide in the early phase after pancreatic islet transplantation did not promote revascularization of transplanted islet grafts.
皮下空间是胰岛移植的理想部位。然而，主要障碍之一是血管再生不良。近来，胰高血糖素样肽1（GLP-1）类似物作为2型糖尿病患者的一种新治疗选择正在兴起，因为它们已被证明可减少β细胞凋亡。因此，我们推测在早期给予GLP-1类似物可能通过减少移植胰岛内外血管内皮细胞的凋亡变化来促进移植胰岛的血管再生。在本研究中，我们使用高灵敏度成像系统评估了GLP-1类似物利拉鲁肽对皮下部位血管再生的影响。我们将背部皮褶小室（DSC）技术与多光子激光扫描显微镜（MPLSM）相结合。
从C57BL/6-Tg（CAG-EGFP）小鼠分离的供体胰岛同基因移植到安装在受体小鼠身上的背部皮褶小室中。作为受体的雄性C57BL/6N小鼠分为3组：对照组、供体胰岛处理组和受体处理组。在供体胰岛处理组中，胰岛用利拉鲁肽（1μmol/L）培养24小时。受体处理组小鼠每天皮下注射利拉鲁肽（100μg/kg）两次，共8天。在第1、4和7天用MPLSM对胰岛移植物周围新形成血管的时间依赖性变化进行成像。为了评估胰岛移植物的血管再生，我们用Volocity系统测量胰岛周围的血管体积。
胰岛移植后的前4天，3组之间新形成血管未检测到显著差异。移植后7天的增加率也未检测到显著差异。
在本研究中，胰岛移植后早期给予GLP-1类似物利拉鲁肽并未促进移植胰岛移植物的血管再生。
