Fructose and uric acid in diabetic nephropathy.
Fructose and uric acid in diabetic nephropathy.
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DOI：
10.1007/s00125-015-3650-4
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发表时间：
2015-09
期刊：
影响因子：
8.2
通讯作者：
Nakagawa T
中科院分区：
文献类型：
--
作者：
Bjornstad P;Lanaspa MA;Ishimoto T;Kosugi T;Kume S;Jalal D;Maahs DM;Snell-Bergeon JK;Johnson RJ;Nakagawa T
临床研究报告了血清尿酸水平与糖尿病肾病的发展之间的关联，但潜在的机制仍然难以捉摸。动物研究的证据表明，阻止尿酸的产生可以保护肾脏免受肾小管间质损伤，这可能表明尿酸在糖尿病肾小管损伤的发生中具有因果作用。反过来，当糖尿病中通过多元醇途径内源产生的果糖被代谢时，由 ATP 消耗和嘌呤核苷酸周转驱动的侧链反应会产生尿酸。因此，内源性果糖产生的尿酸可能会导致糖尿病肾小管间质损伤。因此，我们的研究小组最近证明，阻断糖尿病小鼠模型中的果糖代谢可以通过降低肾小管尿酸的产生来减轻肾小管间质损伤的发展。在这篇综述中，我们讨论了尿酸和果糖之间的关系作为糖尿病肾小管损伤发生的新机制。
Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury.