Thiazolidinedione-induced fluid retention: recent insights into the molecular mechanisms.
Thiazolidinedione-induced fluid retention: recent insights into the molecular mechanisms.
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DOI：
10.1155/2013/628628
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发表时间：
2013
期刊：
影响因子：
2.9
通讯作者：
Włodarczyk M
中科院分区：
文献类型：
--
作者：
Bełtowski J;Rachańczyk J;Włodarczyk M
过氧化物酶体增殖物激活受体γ (PPARγ)激动剂如罗格列酮和吡格列酮用于改善糖尿病患者的胰岛素敏感性。然而，噻唑烷二酮引起液体潴留、水肿，有时在一部分患者中诱发或加重心力衰竭。噻唑烷二酮诱导液体潴留的机制是有争议的。大多数研究表明，这种影响是由于肾小管钠和水的重吸收增加，但具体的肾单位段和钠载体所起的作用尚不清楚。一些研究表明，PPARγ激动剂通过激活上皮Na+通道（ENaC）直接或通过血清和糖皮质激素调节的激酶-1 （SGK-1）刺激Na+在收集管中的再吸收。然而，其他研究并未证实这一机制，甚至报道了ENaC的抑制。收集管的其他机制包括刺激非enac钠通道或抑制氯离子分泌到管腔。此外，噻唑烷二酮可能通过刺激Na+/H+交换体-3和基底侧Na+-HCO3 -共转运体以及Na+，K+- atp酶的表达和活性来增加近端小管的钠重吸收。这些作用是由ppar γ诱导的表皮生长因子受体和下游细胞外信号调节激酶（ERK）的非基因组转激活介导的。
Peroxisome proliferator-activated receptor-γ (PPARγ) agonists such as rosiglitazone and pioglitazone are used to improve insulin sensitivity in patients with diabetes mellitus. However, thiazolidinediones induce fluid retention, edema, and sometimes precipitate or exacerbate heart failure in a subset of patients. The mechanism through which thiazolidinediones induce fluid retention is controversial. Most studies suggest that this effect results from the increase in tubular sodium and water reabsorption in the kidney, but the role of specific nephron segments and sodium carriers involved is less clear. Some studies suggested that PPARγ agonist stimulates Na+ reabsorption in the collecting duct by activating epithelial Na+ channel (ENaC), either directly or through serum and glucocorticoid-regulated kinase-1 (SGK-1). However, other studies did not confirm this mechanism and even report the suppression of ENaC. Alternative mechanisms in the collecting duct include stimulation of non-ENaC sodium channel or inhibition of chloride secretion to the tubular lumen. In addition, thiazolidinediones may augment sodium reabsorption in the proximal tubule by stimulating the expression and activity of apical Na+/H+ exchanger-3 and basolateral Na+-HCO3 − cotransporter as well as of Na+,K+-ATPase. These effects are mediated by PPARγ-induced nongenomic transactivation of the epidermal growth factor receptor and downstream extracellular signal-regulated kinases (ERK).
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影响因子：
3
作者：
Bettowski, J.;Wojcicka, G.;Marciniak, A.
通讯作者：
Marciniak, A.
DOI：
10.1152/ajprenal.00306.2011
发表时间：
2012-03-01
影响因子：
4.2
作者：
Borsting, Emily;Cheng, Vicki Pei-Chun;Cunard, Robyn
通讯作者：
Cunard, Robyn
影响因子：
2.9
作者：
Bourg, Catherine A.;Phillips, Beth Bryles
通讯作者：
Phillips, Beth Bryles
影响因子：
5.8
作者：
Jamroz-Wisniewska, Anna;Wojcicka, Grazyna;Beltowski, Jerzy
通讯作者：
Beltowski, Jerzy
影响因子：
2.9
作者：
Pavlov TS;Imig JD;Staruschenko A
通讯作者：
Staruschenko A