Islet transplantation is a therapeutic option for type 1 diabetes but its long-term success is limited by islet allograft survival. Many factors imperil islet survival, especially the adverse effects and toxicity due to clinical immunosuppressants. Compound K (Cpd K) is a synthesized analog of highly unsaturated fatty acids from Isatis tinctoria L. (Cruciferae). Here we investigated the therapeutic effect of Cpd K in diabetic mice and found that it significantly prolonged islet allograft survival with minimal adverse effects after 10 days. Furthermore, it reduced the proportion of CD4+ and CD8+ T cells in spleen and lymph nodes, inhibited lymphocyte infiltration in allografts, suppressed serum IL-2 and IFN-γ secretion, and increased TGF-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin (Rapa) had a synergistic effect. Cpd K suppressed proliferation of naive T cells by inducing T cell anergy and promoting the generation of regulatory T cells (Tregs). In addition, NF-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effective on islet transplantation.
# P-F M and J J contributed equally to this work.
- Received January 3, 2014.
- Accepted May 13, 2014.
- © 2014 by the American Diabetes Association.
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