ArticleClinical science (London, England : 1979)2012
Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic syndrome: role of insulin.
Article in Clinical science (London, England : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 59 citations in OpenAlex.
- No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.The Biochemical journal · 2026Review
- Insulin-mediated impairment of NCC responsiveness in diet-induced obesity: a new link to salt-sensitive hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Diet-induced obesity impairs salt-dependent downregulation of NCC activity.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- WNKs regulate mouse behavior and alter central nervous system glucose uptake and insulin signaling.bioRxiv : the preprint server for biology · 2025Article
- Hypomagnesemia: exploring its multifaceted health impacts and associations with blood pressure regulation and metabolic syndrome.Diabetology & metabolic syndrome · 2025Review
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
- NCC regulation by WNK signal cascade.Frontiers in physiology · 2022Review
- Kidney and epigenetic mechanisms of salt-sensitive hypertension.Nature reviews. Nephrology · 2021Review
- Role of Rho in Salt-Sensitive Hypertension.International journal of molecular sciences · 2021Review
- WNK4 kinase: from structure to physiology.American journal of physiology. Renal physiology · 2021Review
- Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice.Pflugers Archiv : European journal of physiology · 2021Article
- Magnesium and Hypertension in Old Age.Nutrients · 2020Review
- The WNK signaling pathway and salt-sensitive hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Review
- The interplay of renal potassium and sodium handling in blood pressure regulation: critical role of the WNK-SPAK-NCC pathway.Journal of human hypertension · 2019Review
- Inhibition of Sodium Glucose Cotransporter 2 Attenuates the Dysregulation of Kelch-Like 3 and NaCl Cotransporter in Obese Diabetic Mice.Journal of the American Society of Nephrology : JASN · 2019Article
- Postprandial Effects on ENaC-Mediated Sodium Absorption.Scientific reports · 2019Article
- Impaired pressure natriuresis and non-dipping blood pressure in rats with early type 1 diabetes mellitus.The Journal of physiology · 2019Article
- WNK pathways in cancer signaling networks.Cell communication and signaling : CCS · 2018Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In the present study, we investigated the activity of the thiazide-sensitive NCC (Na(+)-Cl(-) co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12-week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL (Zucker lean) control animals, together with renal NCC expression and molecular markers of NCC activity, such as localization and phosphorylation. Effects of insulin were studied further in mammalian cell lines with inducible and endogenous expression of this molecule. ZO rats displayed marked hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ were enhanced compared with ZL rats, and were associated with a decrease in BP (blood pressure). ZO rats displayed enhanced Thr(53) NCC phosphorylation and predominant membrane localization of both total and phosphorylated NCC, together with a different profile in expression of SPAK (Ste20-related proline/alanine-rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase) inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but delayed compared with the time course of NCC phosphorylation. In summary, we report increased NCC activity in hyperinsulinaemic rodents in conjunction with the SPAK expression profile consistent with NCC activation and reduced WNK4, as well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro. Together, these findings indicate that hyperinsulinaemia is an important driving force of NCC activity in the metabolic syndrome with possible consequences for BP regulation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.