AUTHOR=Wang Chen , Wu Junhong , Wang Yan , Huang Chengcheng , Wei Mengjuan , Zhang Yufei , Shen Renchu , Wang Jingwu 

TITLE=The role of dysregulated copper metabolism in diabetes and its complications: a review

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1681001

DOI=10.3389/fendo.2025.1681001

ISSN=1664-2392

ABSTRACT=Copper (Cu) is an essential trace element for the human body. It significantly affects physiological and pathological processes by regulating various biological pathways, such as mitochondrial proteolipid acylation and glycolysis. Abnormal distribution, excess, or deficiency of Cu can trigger and accelerate the progression of diabetes mellitus (DM) and its complications through redox imbalance and activation of inflammatory pathways. In 2022, a novel form of programmed cell death termed cuproptosis was first identified by Peter Tsvetkov’s team. Increasing evidence indicates that patients with DM exhibit Cu dysregulation, suggesting that Cu dysregulation, exemplified by cuproptosis, might contribute to the pathogenesis of DM and its complications. Notably, regulating Cu metabolic homeostasis has demonstrated efficacy in delaying cancer progression. Similarly, preliminary studies on DM suggest that restoring Cu balance could ameliorate pathological cell death mediated by cuproptosis and oxidative stress. This approach represents a promising therapeutic strategy for DM and its associated complications. Therefore, this review summarizes recent advances regarding Cu dysregulation in DM patients, highlighting the significance of Cu homeostasis across multiple lesion sites associated with DM. Additionally, based on current evidence, this article discusses the regulatory role of Cu dysregulation in DM. Furthermore, we explore the potential molecular mechanisms underlying Cu dysregulation in DM, aiming to identify novel targets for therapeutic intervention.