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Intraportal Transplantation of Pancreatic Islets in Mouse Model
Published on: May 5, 2018
Effects of Dipeptidyl Peptidase-4 Inhibition with MK-0431 on Syngeneic Mouse Islet Transplantation
Jyuhn-Huarng Juang1, Chien-Hung Kuo2, Ying-Hsiu Liu1
1Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung University and Chang Gung Memorial Hospital, 5 Fu-Shin Street, Kweishan, Taoyuan 33305, Taiwan.
Abstract:
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 = 21) or without (n = 17) 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.
Insights
Dipeptidyl peptidase (DPP)-4 inhibition with MK-0431 did not improve islet graft outcomes in diabetic mice receiving a limited number of islets. The treatment showed no significant benefit for blood glucose control or graft beta-cell mass.
Area of Science:
- Endocrinology
- Immunology
- Transplantation Biology
Background:
- Dipeptidyl peptidase (DPP)-4 inhibitors enhance incretin hormones, potentially aiding beta-cell function and survival.
- Islet transplantation is a potential therapy for type 1 diabetes, but graft survival remains a challenge, especially with limited islet mass.
Purpose of the Study:
- To evaluate the efficacy of DPP-4 inhibition using MK-0431 in improving islet graft outcomes in diabetic mice with a marginal islet transplant.
- To assess the impact of MK-0431 on glycemic control, graft beta-cell mass, and insulin content post-islet transplantation.
Main Methods:
- Syngeneic islet transplantation of 150 C57BL/6 mouse islets into streptozotocin-diabetic mice.
- Treatment with MK-0431 (30 mg/kg/day) or placebo for 6 weeks post-transplantation.
- Monitoring of blood glucose, intraperitoneal glucose tolerance tests, body weight, and assessment of graft beta-cell mass and insulin content.
Main Results:
- Both MK-0431-treated and control groups showed decreased blood glucose post-transplantation.
- No significant differences were observed in blood glucose levels, glucose tolerance, or body weight between the groups.
- Graft beta-cell mass and insulin content at 6 weeks were comparable in both treatment and control groups.
Conclusions:
- Post-transplant DPP-4 inhibition with MK-0431 does not enhance the outcome of islet transplantation in diabetic recipients receiving a marginal islet graft.
- The study suggests that DPP-4 inhibition may not be a beneficial strategy for improving islet graft survival or function under these specific experimental conditions.
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