Extra-renal role of urate transporter-1 in diabetes.

The rising global incidence of diabetes mellitus (DM) and hyperuricemia presents a growing challenge to public health systems worldwide. Urate transporter-1 (URAT1), a key renal urate transporter, has emerged as a promising therapeutic target for managing DM and its associated complications. Growing evidence suggests that URAT1's role in metabolic disorders extends beyond its function in the kidney. Specifically, URAT1 can influence uric acid metabolism in multiple tissues including neural, hepatic, vascular smooth muscle, cardiac, and adipose tissue, thereby contributing to insulin resistance, inflammation, and end-organ damage. In this review, we comprehensively examine the extra-renal functions of URAT1, focusing on its roles in the hematopoietic system, heart, liver, adipose tissue, and vascular endothelium in the context of DM. This analysis highlights the multi-organ mechanisms through which URAT1 exerts its effects, offering valuable insights into its potential as a therapeutic target for this complex systemic metabolic disorder.