Effects of Glucagon-Like Peptide 1 Analogue on the Early Phase of Revascularization of Transplanted Pancreatic Islets in a Subcutaneous Site

Abstract Objective 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). Methods 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. Results 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. Conclusions 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.