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Updated: Jul 16, 2025
Regulatory T cells: Therapeutic Potential for Treating Transplant Rejection and Type I Diabetes
Published on: August 20, 2007
Nrf2: Therapeutic target of islet function protection in diabetes and islet transplantation
Butian Wei1, Xin Zhang1, Jiwei Qian1
1Department of general Surgery, The Fourth affiliated Hospital, Zhejiang university School of Medicine, Yiwu 322000, China.
Abstract:
Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been reported as a major intracellular regulator of antioxidant stress, notably in islet β cells with low antioxidant enzyme content. Nrf2 is capable of regulating antioxidant function, while it can also regulate insulin secretion, proliferation, and differentiation of β cells, ER stress, as well as mitochondrial function. Thus, Nrf2 pharmacological activators have been employed in the laboratory for the treatment of diabetic mice. Islet cells are exposed to oxidative environment when islet is being transplanted. Accordingly, less than 50% of islet cells are well transplanted, and their normal function is maintained. The pharmacological activation of Nrf2 has been confirmed to protect islet cells at different stages of transplantation stages during experiments for islet transplantation.
Insights
Nuclear factor-erythroid 2-related factor 2 (Nrf2) protects islet cells from oxidative stress during transplantation. Activating Nrf2 enhances islet cell function and survival, offering a potential therapeutic strategy for diabetes.
Area of Science:
- Endocrinology
- Cell Biology
- Transplantation Immunology
Background:
- Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key regulator of cellular antioxidant responses, particularly relevant in pancreatic islet beta cells due to their inherent low antioxidant enzyme levels.
- Nrf2 influences critical beta cell functions including insulin secretion, proliferation, differentiation, endoplasmic reticulum stress, and mitochondrial function.
Purpose of the Study:
- To investigate the protective role of pharmacological Nrf2 activation in islet cells during the transplantation process.
- To evaluate the efficacy of Nrf2 activators in preserving islet cell function and survival under oxidative stress conditions encountered during transplantation.
Main Methods:
- Utilized laboratory experiments involving Nrf2 pharmacological activators in the context of islet transplantation models.
- Assessed the impact of Nrf2 activation on islet cell viability, function, and survival at various stages of the transplantation procedure.
Main Results:
- Pharmacological activation of Nrf2 demonstrated a protective effect on islet cells subjected to the oxidative environment of transplantation.
- Nrf2 activation was confirmed to safeguard islet cells throughout different phases of experimental islet transplantation, improving their functional maintenance.
Conclusions:
- Pharmacological Nrf2 activation is a promising strategy to enhance the success of islet transplantation by mitigating oxidative stress.
- Targeting Nrf2 pathways could improve graft survival and long-term function of transplanted islet cells, offering a potential therapeutic avenue for diabetes treatment.
