Serum Uric Acid as a Mediator of Insulin Resistance: Molecular Mechanisms and Metabolic Pathways

Emerging evidence indicates that elevated SUA levels are associated with disturbances in insulin signaling pathways. Mechanistically, high SUA levels can lead to oxidative stress, endothelial dysfunction, inflammation, and impaired function of adipocytes-all of which collectively impede insulin receptor activity and downstream signaling. Key pathways involved include activation of the NLRP3 inflammasome, suppression of AMP-activated protein kinase (AMPK), and induction of mitochondrial dysfunction. These mechanisms contribute to altered insulin sensitivity in both hepatic and adipose tissues. Clinically, higher SUA levels are associated with increased risk of developing metabolic syndrome, T2D, and cardiovascular diseases, highlighting SUA's potential as both a biomarker and a therapeutic target. Despite these findings, the precise molecular interactions between SUA and insulin signaling remain incompletely understood, underscoring the need for further translational and mechanistic research.