Background
    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.

Aim
    In this study, we compared the effects of dipeptidyl peptidase-4 inhibitor LAF237 on diabetic recipients transplanted with a marginal or sufficient number of islets.

Method
    We syngeneically transplanted 150 or 300 C57BL/6 mouse islets under the kidney capsule of each streptozotocin-diabetic mouse, and then treated recipients with distilled water or LAF237 (10 mg/kg/day, po) for 6 weeks.

Results
    In mice transplanted with 150 islets, there were no significant differences between LAF237-treated and control group in terms of blood glucose, body weights, the area under the curve (AUC) of intraperitoneal glucose tolerance test (IPGTT) at 2, 4 and 6 weeks as well as the graft insulin content and β-cell mass at 6 weeks. In mice transplanted with 300 islets, blood glucose levels and body weights were not significantly different between LAF237-treated group and controls. However, the AUC of IPGTT was lower in the LAF237-treated group than controls at 4 and 6 weeks (p=0.033 and 0.015, respectively). At 6 weeks, LAF237-treated group had more graft β-cell mass than controls (p=0.043) although the graft insulin content was comparable between two groups.

Discussion
    Our results indicate posttransplant LAF237 treatment improves glucose tolerance and expands graft β-cell mass in diabetic recipients transplanted with a sufficient but not marginal number of islets.

LAF237 enhances glucose tolerance and graft β-cell mass in diabetic mice transplanted with sufficient numbers of islets