AUTHOR=Baumel-Alterzon Sharon , Scott Donald K. 

TITLE=Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells

JOURNAL=Frontiers in Endocrinology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1011187

DOI=10.3389/fendo.2022.1011187

ISSN=1664-2392

ABSTRACT=<p>The beta-cell identity gene, pancreatic duodenal homeobox 1 (<italic>Pdx1</italic>), plays critical roles in many aspects of the life of beta-cells including differentiation, maturation, function, survival and proliferation. High levels of reactive oxygen species (ROS) are extremely toxic to cells and especially to beta-cells due to their relatively low expression of antioxidant enzymes. One of the major mechanisms for beta-cell dysfunction in type-2 diabetes results from oxidative stress-dependent inhibition of PDX1 levels and function. ROS inhibits Pdx1 by reducing <italic>Pdx1</italic> mRNA and protein levels, inhibiting PDX1 nuclear localization, and suppressing PDX1 coactivator complexes. The nuclear factor erythroid 2-related factor (<italic>Nrf2</italic>) antioxidant pathway controls the redox balance and allows the maintenance of high Pdx1 levels. Therefore, pharmacological activation of the <italic>Nrf2</italic> pathway may alleviate diabetes by preserving Pdx1 levels.</p>