Peroxiredoxin/thioredoxin in beta-cells


We demonstrated in 2019 (J. Biol. Chem.) and 2020 (Am. J. Physiol.) that peroxiredoxins, thioredoxin, and thioredoxin reductase are essential antioxidants in pancreatic β-cells. They protect these cells from oxidants like hydrogen peroxide and peroxynitrite. 
Thioredoxin/peroxiredoxin antioxidant cycle. Peroxiredoxin (Prx) reduces hydrogen peroxide to water by using a series of disulfide exchanges with thioredoxin (Trx) and thioredoxin reductase (TrxR). Reducing equivalents are provided by NADPH.
Our 2022 publication in Function demonstrated that inhibition or deletion of thioredoxin reductase (TrxR) blunts insulin secretion and decreases expression of identity factors in β-cells.

We want to understand the relationship between the TrxR pathway and β-cell function and identity and determine if impairment of this pathway is related to the decline of β-cell function in type 2 diabetes.

One branch of this project focuses on TrxR1 and the other branch focuses on Prx1. 

To explore this pathway, we utilize both pharmacological and genetic tools in an insulinoma cell line, primary mouse and human pancreatic islets, and mouse models. 

Publications


Deletion of Thioredoxin Reductase Disrupts Redox Homeostasis and Impairs β-Cell Function


Jennifer S. Stancill, Polly A. Hansen, A. Mathison, E. Schmidt, J. Corbett

Function, 2022


The Role of Thioredoxin/Peroxiredoxin in the β-Cell Defense Against Oxidative Damage


Jennifer S. Stancill, J. Corbett

Frontiers in Endocrinology, 2021


Peroxiredoxin 1 plays a primary role in protecting pancreatic ß-cells from hydrogen peroxide and peroxynitrite.


Jennifer S. Stancill, John T. Happ, Katarzyna A. Broniowska, N. Hogg, J. Corbett

American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 2020


Pancreatic β-cells detoxify H2O2 through the peroxiredoxin/thioredoxin antioxidant system


Jennifer S. Stancill, Katarzyna A. Broniowska, Bryndon J. Oleson, Aaron Naatz, J. Corbett

Journal of Biological Chemistry, 2019



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