title: Linking uric acid metabolism to diabetic complications.
abstract: Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.
authors.affiliation: Akifumi Kushiyama, Kentaro Tanaka, Shigeko Hara, Shoji Kawazu, Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Tokyo 103-0002, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Akifumi Kushiyama, Kentaro Tanaka, Shigeko Hara, Shoji Kawazu, Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Tokyo 103-0002, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Akifumi Kushiyama, Kentaro Tanaka, Shigeko Hara, Shoji Kawazu, Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Tokyo 103-0002, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Hara
authors.affiliation: Akifumi Kushiyama, Kentaro Tanaka, Shigeko Hara, Shoji Kawazu, Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Tokyo 103-0002, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kawazu
keywords: Diabetes mellitus; Diabetic complications; Metabolism; Uric acid; Xanthine dehydrogenase/xanthine oxidase; Xanthine oxidase inhibitor