| Abstract: | Background and aims: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase circulating levels of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which promote β -cell proliferation and survival. This study tested if DPP-4 inhibition with LAF237 is beneficial for diabetic recipients with a marginal or sufficient number of islets. Materials and methods:We syngeneically transplanted 150 or 300 C57BL/6 mouse islets under the kidney capsule of each inbred streptozotocin-diabetic mouse, and then treated recipients with or without LAF237 (10 mg/kg, po) for 6 weeks. Before and after transplantation, recipients’ blood glucose, body weight and intraperitoneal glucose tolerance test (IPGTT) were measured. At 6 weeks, the grafts were removed to determine insulin content and β-cell mass. Results:In mice transplanted with 150 islets, blood glucose levels decreased in both groups after transplantation, but there were no significant differences between two groups. The area under the curve (AUC) of IPGTT at 2, 4 and 6 weeks were comparable between the LAF237-treated group and controls. Both groups exhibited increased body weights over time, but the differences between two groups were not significant. At 6 weeks after transplantation, the graft insulin content and β-cell mass of grafts were not significantly different between LAF237-treated group and controls. In mice transplanted with 300 islets, blood glucose levels decreased in both groups after islet transplantation, but there were no significant differences between two groups. The AUC of IPGTT at 4 and 6 weeks was lower in the LAF237-treated group than controls (28720 ± 1780 vs. 34840 ± 2136 mg-min, p=0.033 and 26330 ± 1748 vs. 33340 ± 2125 mg-min, p=0.015, respectively). Both groups exhibited increased body weights over time, but the differences between two groups were not significant. At 6 weeks after transplantation, the insulin content of grafts was not significantly different between LAF237-treated group and controls. However, LAF237-treated group had more graft β-cell mass than controls (0.53±0.09 vs. 0.31±0.06 mg, p=0.043). Conclusion:Our results indicate posttransplant LAF237 treatment improves glucose tolerance and expands graft β-cell mass in diabetic recipients transplanted with a sufficient number of islets. |
