ArticleNephron2015
PPARγ agonist-induced fluid retention depends on αENaC expression in connecting tubules.
Article in Nephron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- A double-blind, Randomized controlled trial on glucose-lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase-4 inhibitor therapy: REFIND study.Diabetes, obesity & metabolism · 2022 · on this mapTrial
- Article
- Urine Di-(2-ethylhexyl) Phthalate Metabolites Are Independently Related to Body Fluid Status in Adults: Results from a U.S. Nationally Representative Survey.International journal of environmental research and public health · 2022Article
- 2020 Consensus of Taiwan Society of Cardiology on the pharmacological management of patients with type 2 diabetes and cardiovascular diseases.Journal of the Chinese Medical Association : JCMA · 2020Article
- Thiazolidinediones: the Forgotten Diabetes Medications.Current diabetes reports · 2019Review
- Rosiglitazone promotes ENaC-mediated alveolar fluid clearance in acute lung injury through the PPARγ/SGK1 signaling pathway.Cellular & molecular biology letters · 2019Article
- Unmasking a sustained negative effect of SGLT2 inhibition on body fluid volume in the rat.American journal of physiology. Renal physiology · 2018Article
- Fluid Retention Caused by Rosiglitazone Is Related to Increases in AQP2 andPPAR research · 2017Article
- Glucose dysregulation and response to common anti-diabetic agents in the FATZO/Pco mouse.PloS one · 2017Article
- Renal tubular epithelium-targeted peroxisome proliferator-activated receptor-γ maintains the epithelial phenotype and antagonizes renal fibrogenesis.Oncotarget · 2016Article
- The function and regulation of acid-sensing ion channels (ASICs) and the epithelial Na(+) channel (ENaC): IUPHAR Review 19.British journal of pharmacology · 2016Review
- ENaC activity in collecting ducts modulates NCC in cirrhotic mice.Pflugers Archiv : European journal of physiology · 2015Article
- Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention.PPAR research · 2015Review
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
aimsThiazolidinediones (TZDs, like rosiglitazone (RGZ)) are peroxisome proliferator-activated receptor γ (PPARγ) agonists used to treat type 2 diabetes. Clinical limitations include TZD-induced fluid retention and body weight (BW) increase, which are inhibited by amiloride, an epithelial-sodium channel (ENaC) blocker. RGZ-induced fluid retention is maintained in mice with αENaC knockdown in the collecting duct (CD). Since ENaC in the connecting tubule (CNT) rather than in CD appears to be critical for normal NaCl retention, we aimed to further explore the role of ENaC in CNT in RGZ-induced fluid retention.
methodsMice with conditional inactivation of αENaC in both CNT and CD were used (αENaC lox/lox AQP2-Cre; 'αENaC-CNT/CD-KO') and compared with littermate controls (αENaC lox/lox mice; 'WT'). BW was monitored and total body water (TBW) and extracellular fluid volume (ECF) were determined by bioelectrical impedance spectroscopy (BIS) before and after RGZ (320 mg/kg diet for 10 days).
resultsOn regular NaCl diet, αENaC-CNT/CD-KO had normal BW, TBW, ECF, hematocrit, and plasma Na(+), K(+), and creatinine, associated with an increase in plasma aldosterone compared with WT. Challenging αENaC-CNT/CD-KO with a low NaCl diet unmasked impaired NaCl and K homeostasis, consistent with effective knockdown of αENaC. In WT, RGZ increased BW (+6.1%), TBW (+8.4%) and ECF (+10%), consistent with fluid retention. These changes were significantly attenuated in αENaC-CNT/CD-KO (+3.4, 1.3, and 4.3%).
conclusionTogether with the previous studies, the current results are consistent with a role of αENaC in CNT in RGZ-induced fluid retention, which dovetails with the physiological relevance of ENaC in this segment.
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