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Diabetes. 2014 Oct;63(10):3458-69. doi: 10.2337/db14-0012. Epub 2014 May 16.

Immunosuppressive effect of compound K on islet transplantation in an STZ-induced diabetic mouse model.

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  • 1Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China.
  • 2Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen City, Fujian Province, PR China.
  • 3State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen City, Fujian Province, PR China.
  • 4Department of Pathology, The Affiliated Chenggong Hospital of Xiamen University, Xiamen City, Fujian Province, PR China.
  • 5Department of Hepatobiliary Internal Medicine Clinic, The Affiliated Fuzhou Second Hospital of Xiamen University, Fuzhou City, Fujian Province, PR China.
  • 6School of Pharmaceutical Sciences, Guangxi Medical University, Nanning City, Guangxi Province, PR China.
  • 7Organ Transplantation Institute, Medical College, Xiamen University, Xiamen City, Fujian Province, PR China xia@xmu.edu.cn oti@xmu.edu.cn.

Abstract

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 (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 inflammatory cell infiltration in allografts, suppressed serum interleukin-2 and interferon-γ secretion, and increased transforming growth factor-β and Foxp3 mRNA expression. Surprisingly, Cpd K and rapamycin had a synergistic effect. Cpd K suppressed proliferation of naïve T cells by inducing T-cell anergy and promoting the generation of regulatory T cells. In addition, nuclear factor-κB signaling was also blocked. Taken together, these findings indicate that Cpd K may have a potential immunosuppressant effect on islet transplantation.

© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

[PubMed - indexed for MEDLINE]
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