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Updated: May 9, 2026
Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice
Published on: July 23, 2017
A new cell-permeable peptide allows successful allogeneic islet transplantation in mice
Hirofumi Noguchi1, Masayuki Matsushita, Teru Okitsu
1Department of Physiology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558 Japan.
Abstract:
Calcineurin inhibitors such as cyclosporine A and FK506 have been used for transplant therapy and treatment of autoimmune diseases. However, the inhibition of calcineurin outside the immune system has a number of side effects, including hyperglycemia. In the search for safer drugs, we developed a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells) using the polyarginine peptide delivery system. This peptide provided immunosuppression for fully mismatched islet allografts in mice. In addition, it did not affect insulin secretion, whereas FK506 caused a dose-dependent decrease in insulin secretion. Cell-permeable peptides can thus provide a new strategy for drug development and may eventually be useful clinically.
Insights
Researchers developed a novel cell-permeable peptide inhibitor of the nuclear factor of activated T cells (NFAT). This peptide offers immunosuppression without affecting insulin secretion, unlike current calcineurin inhibitors.
Area of Science:
- Immunology
- Pharmacology
- Drug Development
Background:
- Calcineurin inhibitors (e.g., cyclosporine A, FK506) are used for transplant therapy and autoimmune diseases.
- Off-target calcineurin inhibition causes side effects like hyperglycemia.
- Need for safer immunosuppressive agents is critical.
Purpose of the Study:
- To develop a cell-permeable inhibitor of NFAT (nuclear factor of activated T cells).
- To evaluate the efficacy and safety of this novel inhibitor in an allograft model.
- To compare its effects on insulin secretion with existing drugs.
Main Methods:
- Development of a cell-permeable NFAT inhibitor using a polyarginine peptide delivery system.
- Testing the inhibitor's immunosuppressive capacity in a mouse model of fully mismatched islet allografts.
- Assessing the impact of the inhibitor and FK506 on insulin secretion in vitro.
Main Results:
- The cell-permeable NFAT inhibitor successfully induced immunosuppression for islet allografts in mice.
- Unlike FK506, the novel peptide did not impair insulin secretion.
- FK506 demonstrated a dose-dependent reduction in insulin secretion.
Conclusions:
- Cell-permeable peptides represent a promising new strategy for developing safer immunosuppressive drugs.
- This approach may overcome the side effects associated with traditional calcineurin inhibitors.
- The developed peptide inhibitor shows potential for future clinical applications in transplantation and autoimmune diseases.
