Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory.
Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory.
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DOI：
10.1038/srep40544
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发表时间：
2017-01-12
影响因子：
4.6
通讯作者：
de M Loureiro AP
中科院分区：
文献类型：
--
作者：
de Oliveira AA;de Oliveira TF;Bobadilla LL;Garcia CC;Berra CM;de Souza-Pinto NC;Medeiros MH;Di Mascio P;Zatz R;de M Loureiro AP
在糖尿病患者中，即使在血糖得到适当处理后，也会发生持续很长一段时间的生化变化，这是一种有趣的现象，称为代谢记忆。在这项研究中，我们证明了糖尿病大鼠的肾脏通路在糖尿病过程中逐渐改变，并在晚期血糖控制后保持持续改变。这一途径包括早期尿酸清除和pAMPK表达下降，随后富马酸积累，转化生长因子-β表达增加，pGC-1α表达降低，线粒体DNA甲基化和羟甲基化下调。糖尿病治疗后尿酸清除量持续下降可能是血糖控制后肾脏生化改变延长的原因之一，其调节机制可能与AMPK活性持续下降和炎症反应有关。这篇手稿首次提出了高尿酸血症的可能作用以及血糖控制后作为代谢记忆的一部分的潜在生化变化在糖尿病肾病发生发展中的作用。
The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control.