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Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation

Department of Surgery, University of California, Irvine, CA 92868, USA
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(4), 321;
Received: 15 March 2020 / Revised: 12 April 2020 / Accepted: 14 April 2020 / Published: 16 April 2020
(This article belongs to the Special Issue Keap1/Nrf2 Signaling Pathway)
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. View Full-Text
Keywords: Nrf2/Keap1; antioxidant; diabetes; pancreatic islet; transplantation Nrf2/Keap1; antioxidant; diabetes; pancreatic islet; transplantation
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Jarrin Lopez, A.; Lau, H.; Li, S.; Ichii, H. Potential Benefits of Nrf2/Keap1 Targeting in Pancreatic Islet Cell Transplantation. Antioxidants 2020, 9, 321.

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