Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport.
Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport.
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AKT和SGK1在肾小管运输调节中的作用。
DOI：
10.1155/2015/971697
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发表时间：
2015
影响因子：
--
通讯作者：
Horita S
中科院分区：
文献类型：
--
作者：
Satoh N;Nakamura M;Suzuki M;Suzuki A;Seki G;Horita S
丝氨酸/苏氨酸激酶Akt是包括调节肾小管转运在内的多种信号通路的关键介体。在近端小管，Akt通过胰岛素受体底物2(IRS2)介导胰岛素信号转导，并刺激小苏打转运蛋白(NBCe1)，导致钠重吸收增加。在胰岛素抵抗中，肾皮质的IRS2异常保留，可能通过钠滞留介导胰岛素对NBCe1的刺激作用，从而导致糖尿病高血压。同样，在远端曲管和皮质集合管中，胰岛素诱导的Akt磷酸化介导了几种激素信号，从而增强了氯化钠共转运体(NCC)和上皮性钠通道(ENaC)的活性，从而增加了钠的重吸收。血清和糖皮质激素诱导的激酶1(SGK1)介导了醛固酮信号转导。胰岛素可刺激SGK1对肾脏转运蛋白产生多种作用。在肾皮质集合管中，SGK1通过抑制ENaC的降解来调节其表达水平。此外，SGK1和Akt通过肾外髓质钾通道(ROMK)协同调节钾的分泌。此外，近端小管钠质子交换蛋白3(NHE3)可能被SGK1激活。本文就Akt和SGK1在调节肾小管转运中的作用的研究进展作一综述。
A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2) and stimulates sodium-bicarbonate cotransporter (NBCe1), resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC) and epithelial sodium channel (ENaC) activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK). Moreover, sodium-proton exchanger 3 (NHE3) in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.