Xanthoceras sorbifolium leaves alleviate hyperuricemic nephropathy by inhibiting the PI3K/AKT signaling pathway to regulate uric acid transport

Liu, Yuchao; Han, Yunqi; Liu, Yuquan; Huang, Congying; Feng, Wanze; Cui, Hongwei; Li, Minhui

doi:10.1016/j.jep.2024.117946

Cited by 2 publications

(1 citation statement)

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“…However, further studies on GLUT9 failed to reproduce GLUT9 as either [42]. GLUT9 expression is almost ubiquitous, with higher levels in the liver, kidney, brain, placenta, lung, and peripheral leukocytes [43]; it is suggested that its expression level is regulated by the insulin and PI3K/AKT signaling pathway [34,44]. Like URAT1, GLUT9 is inhibited by high concentrations of uricosuric drugs like benzbromarone, tranilast, and probenecid in Xenopus oocyte expression systems [31].…”

Section: Glucose Transporter (Glut) 9/slc2a9mentioning

confidence: 99%

Regulation of Urate Homeostasis by Membrane Transporters

Takada,

Miyata,

Toyoda

et al. 2024

GUCDD

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Uric acid is the final purine metabolite in humans. Serum urate levels are regulated by a balance between urate production, mainly in the liver, and its excretion via the kidneys and small intestine. Given that uric acid exists as a urate anion at physiological pH 7.4, membrane transporters are required to regulate urate homeostasis. In the kidney, urate transporter 1, glucose transporter 9, and organic anion transporter 10 contribute to urate reabsorption, whereas sodium-dependent phosphate transport protein 1 would be involved in urate excretion. Other transporters have been suggested to be involved in urate handling in the kidney; however, further evidence is required in humans. ATP-binding cassette transporter G2 (ABCG2) is another urate transporter, and its physiological role as a urate exporter is highly demonstrated in the intestine. In addition to urate, ABCG2 regulates the behavior of endogenous substances and drugs; therefore, the functional inhibition of ABCG2 has physiological and pharmacological effects. Although these transporters explain a large part of the urate regulation system, they are not sufficient for understanding the whole picture of urate homeostasis. Therefore, numerous studies have been conducted to find novel urate transporters. This review provides the latest evidence of urate transporters from pathophysiological and clinical pharmacological perspectives.

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