Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms
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 subse...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2013/628628 |
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| author | Jerzy Bełtowski Jolanta Rachańczyk Mirosław Włodarczyk |
| author_facet | Jerzy Bełtowski Jolanta Rachańczyk Mirosław Włodarczyk |
| author_sort | Jerzy Bełtowski |
| collection | DOAJ |
| description | 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+- 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). |
| format | Article |
| id | doaj-art-5e2ded04236d4c3296de2f97216e32f9 |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
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| series | PPAR Research |
| spelling | doaj-art-5e2ded04236d4c3296de2f97216e32f92025-02-03T00:59:28ZengWileyPPAR Research1687-47571687-47652013-01-01201310.1155/2013/628628628628Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular MechanismsJerzy Bełtowski0Jolanta Rachańczyk1Mirosław Włodarczyk2Department of Pathophysiology, Medical University of Lublin, 8 Jaczewskiego , 20090 Lublin, PolandDepartment of Pathophysiology, Medical University of Lublin, 8 Jaczewskiego , 20090 Lublin, PolandDepartment of Pathophysiology, Medical University of Lublin, 8 Jaczewskiego , 20090 Lublin, PolandPeroxisome 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+- 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).http://dx.doi.org/10.1155/2013/628628 |
| spellingShingle | Jerzy Bełtowski Jolanta Rachańczyk Mirosław Włodarczyk Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms PPAR Research |
| title | Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms |
| title_full | Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms |
| title_fullStr | Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms |
| title_full_unstemmed | Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms |
| title_short | Thiazolidinedione-Induced Fluid Retention: Recent Insights into the Molecular Mechanisms |
| title_sort | thiazolidinedione induced fluid retention recent insights into the molecular mechanisms |
| url | http://dx.doi.org/10.1155/2013/628628 |
| work_keys_str_mv | AT jerzybełtowski thiazolidinedioneinducedfluidretentionrecentinsightsintothemolecularmechanisms AT jolantarachanczyk thiazolidinedioneinducedfluidretentionrecentinsightsintothemolecularmechanisms AT mirosławwłodarczyk thiazolidinedioneinducedfluidretentionrecentinsightsintothemolecularmechanisms |