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World J Diabetes. Jul 15, 2025; 16(7): 107673
Published online Jul 15, 2025. doi: 10.4239/wjd.v16.i7.107673
Extra-renal role of urate transporter-1 in diabetes
Tian-Shu Yang, Min Du, Ling-Yun Luo, Li Lin, Xue-Lian Luo
Tian-Shu Yang, Min Du, Ling-Yun Luo, Li Lin, Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Xue-Lian Luo, Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
Co-first authors: Tian-Shu Yang and Min Du.
Co-corresponding authors: Li Lin and Xue-Lian Luo.
Author contributions: Yang TS wrote the original manuscript; Yang TS and Du M contributed equally to this article and are co-first authors of this manuscript; Yang TS, Du M, Luo LY, Lin L, and Luo XL wrote, reviewed and edited the manuscript; Lin L and Luo XL managed the project; they contributed equally to this article and are co-corresponding authors of manuscript; all authors thoroughly reviewed and endorsed the final manuscript.
Conflict-of-interest statement: The authors report no relevant conflicts of interest for this article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Xue-Lian Luo, MD, PhD, Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Huixing Street, Yubei District, Chongqing 401120, China. 806850653@qq.com
Received: March 28, 2025
Revised: April 20, 2025
Accepted: June 3, 2025
Published online: July 15, 2025
Processing time: 109 Days and 23.7 Hours
Abstract

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.

Keywords: Diabetes mellitus; Insulin resistance; Extra-renal urate transporter-1; Urate transporter-1 inhibitor

Core Tip: Emerging evidence highlights the extra-renal roles of urate transporter-1 (URAT1) in diabetes mellitus, extending beyond its canonical function in renal urate reabsorption. URAT1-mediated uric acid uptake in tissues such as adipose, liver, heart, endothelium, and hematopoietic cells exacerbates insulin resistance, oxidative stress, and inflammation, driving diabetic complications. Pharmacological inhibition of URAT1 with agents like dotinurad, benzbromarone, or probenecid attenuates these pathological processes by reducing uric acid influx, restoring insulin signaling, and suppressing pro-inflammatory pathways. This review underscores URAT1 as a pivotal therapeutic target for mitigating multi-organ dysfunction in diabetes mellitus, offering novel strategies to address systemic metabolic and inflammatory derangements.