Abstract
The accumulation of plasma advanced oxidation protein products (AOPPs) has been linked with diverse disorders, including diabetes, chronic kidney disease, obesity, and metabolic syndrome. The aim of the present study was to evaluate the pathophysiological relevance of AOPPs in β-cell destruction and dysfunction. Exposure of cultured rat β-cells (INS-1) to AOPPs induced an increase in Bax expression, caspase-3 activity, and apoptosis as well as a decrease in Bcl-2 expression in a dose- and time-dependent manner. AOPP challenge rapidly increased the production of intracellular superoxide by activation of NADPH oxidases, demonstrated by p47phox translocation and interaction with p22phox and gp91phox, and this in turn led to apoptosis. AOPPs treatment resulted in β-cell apoptosis, AOPPs accumulation, and decreased insulin content in pancreas and plasma in unilateral nephrectomized rats. Chronic inhibition of NADPH oxidase by apocynin prevented β-cell apoptosis and ameliorated insulin deficiency in AOPP-challenged rats. This study demonstrates for the first time that accumulation of AOPPs promotes NADPH oxidase-dependent β-cell destruction and dysfunction by the Bcl-2/Bax–caspase apoptotic pathway. This finding may provide a mechanistic explanation for β-cell destruction and dysfunction in patients with diverse disorders.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
