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Insulin is a vital hormone for regulating glycemia that often undergoes post\u2010translational modifications during processing from pre\u2010proinsulin to biologically active insulin. While necessary for proper glucose homeostasis, insulin is also an autoantigen recognized by autoreactive T cells in T1D. Cellular stress pathways including endoplasmic reticulum stress and oxidative stress mediated by an increase in reactive oxygen species (ROS) synthesis and\/or a concomitant decrease in antioxidant function can further drive post\u2010translational modifications of various autoantigens in T1D including insulin. Innate immune\u2010derived ROS generation is an essential frontline defense against microbial infections, but ROS can also function as signaling intermediates to properly stimulate T cell responses. Oxidative stress\u2010induced post\u2010translational modifications are thought to trigger autoreactive T cells in T1D by generating novel neoepitopes, eliciting epitope spreading, or enhancing autoantigen interactions with antigen\u2010presenting cells. With the current technology, detecting post\u2010translationally modified proteins is challenging. In this review, we will explore the role of ROS and other post\u2010translational modifications involved in T1D. We will also discuss islet transplantation strategies being used for patients with T1D including novel cell sources for beta\u2010cell replacement and management of oxidative stress after transplantation.<\/jats:p>","DOI":"10.1111\/imr.70182","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T07:53:11Z","timestamp":1792050791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Stress, Post\u2010Translational Modifications, and Type 1 Diabetes Pathogenesis"],"prefix":"10.1111","volume":"343","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1886-4061","authenticated-orcid":false,"given":"Colleen J.","family":"Winstead","sequence":"first","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology University of Kansas Medical Center  Kansas City Kansas 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