Effects of Dipeptidyl Peptidase-4 Inhibition with MK-0431 on Syngeneic Mouse Islet Transplantation

الملخص EN

Dipeptidyl peptidase (DPP)-4 inhibitors increase circulating levels of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which may promote β-cell proliferation and survival.

This study tested if DPP-4 inhibition with MK-0431 is beneficial for diabetic mice syngeneically transplanted with a marginal number of islets.

We syngeneically transplanted 150 C57BL/6 mouse islets under the kidney capsule of each streptozotocin-diabetic mouse and then treated recipients with ( n = 2 1 ) or without ( n = 1 7 ) MK-0431 (30 mg/kg/day, po) for 6 weeks.

After islet transplantation, blood glucose levels decreased in both MK-0431-treated and control groups.

However, the blood glucose and area under the curve of the intraperitoneal glucose tolerance test at 2, 4, and 6 weeks were not significantly different between MK-0431-treated mice and controls.

During 6 weeks, both groups exhibited increased body weights over time.

However, the weight between two groups did not differ throughout the study period.

At 6 weeks after transplantation, the graft beta-cell mass (0.024 ± 0.005 versus 0.023 ± 0.007 mg, P = 0 .

8793 ) and insulin content (140 ± 48 versus 231 ± 63 ng, P = 0 .

2939 ) were comparable in the MK-0431-treated group and controls.

Our results indicate posttransplant DPP-4 inhibition with MK-0431 in the diabetic recipient with a marginal number of islets is not beneficial to transplantation outcome or islet grafts.