Jarrin Lopez Alberto, Lau Hien, Li Shiri, Ichii Hirohito
Department of Surgery, University of California, Irvine, CA 92868, USA.
Antioxidants (Basel). 2020 Apr 16;9(4):321. doi: 10.3390/antiox9040321.
Permanent pancreatic islet cell destruction occurs in type 1 diabetes mellitus (T1DM) through the infiltration of inflammatory cells and cytokines. Loss of β-cell integrity secondary to oxidation leads to an inability to appropriately synthesize and secrete insulin. Allogenic islet cell transplantation (ICT) has risen as a therapeutic option to mitigate problematic hypoglycemia. Nevertheless, during the process of transplantation, islet cells are exposed to oxidatively caustic conditions that severely decrease the islet cell yield. Islet cells are at a baseline disadvantage to sustain themselves during times of metabolic stress as they lack a robust anti-oxidant defense system, glycogen stores, and vascularity. The Nrf2/Keap1 system is a master regulator of antioxidant genes that has garnered attention as pharmacologic activators have shown a protective response and a low side effect profile. Herein, we present the most recently studied Nrf2/Keap1 activators in pancreas for application in ICT: Dh404, dimethyl fumarate (DMF), and epigallocatechin gallate (EGCG). Furthermore, we discuss that Nrf2/Keap1 is a potential target to ameliorate oxidative stress at every step of the Edmonton Protocol.
在1型糖尿病（T1DM）中，永久性胰岛细胞破坏是通过炎症细胞和细胞因子的浸润发生的。氧化继发的β细胞完整性丧失导致无法适当地合成和分泌胰岛素。同种异体胰岛细胞移植（ICT）已成为减轻问题性低血糖的一种治疗选择。然而，在移植过程中，胰岛细胞会暴露于氧化腐蚀性条件下，这会严重降低胰岛细胞产量。胰岛细胞在代谢应激期间维持自身存在基线劣势，因为它们缺乏强大的抗氧化防御系统、糖原储备和血管。Nrf2/Keap1系统是抗氧化基因的主要调节因子，由于药物激活剂已显示出保护作用且副作用小，因此受到关注。在此，我们介绍了胰腺中最近研究的用于ICT的Nrf2/Keap1激活剂：Dh404、富马酸二甲酯（DMF）和表没食子儿茶素没食子酸酯（EGCG）。此外，我们讨论了Nrf2/Keap1是在埃德蒙顿方案的每个步骤中减轻氧化应激的潜在靶点。
