In diet-induced obese mice, prolonged therapeutic selenium supplementation lowered oxidative damage in epididymal fat, restored suppressed levels of the secreted selenoprotein GPX3 and the insulin receptor (InsR), boosted insulin-stimulated AKT phosphorylation, and improved oral glucose tolerance. In human adipose tissue, GPX3 tracks InsR expression across metabolic parameters and rises after weight loss. Recombinant GPX3 induced InsR in pre-adipocytes, fat explants and organoids by increasing SP1 binding to the Insr promoter, and this worked through protein structure rather than selenocysteine-dependent peroxidase activity. The evidence for supplementation is from mice, not humans. The finding is intriguing because antioxidant trials in diabetes have largely disappointed, and this work suggests GPX3 may act less as an antioxidant than as a paracrine signal sustaining insulin sensitivity. That reframing could explain why simply boosting antioxidant defenses fails. The human data are correlational, however, and weight-loss-driven GPX3 increases cannot separate cause from effect. Selenium offers no obvious human takeaway: large trials such as SELECT linked supplementation to higher type 2 diabetes risk in selenium-replete adults, and mouse doses called therapeutic may not translate. This preprint has not been peer reviewed, so conclusions may change. Editorially, it is a mechanistic advance that raises GPX3 as a drug target, not guidance to supplement selenium.