ArticleAmerican journal of physiology. Renal physiology2009
Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells.
Article in American journal of physiology. Renal physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 77 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Clinical, Morphometric and Biochemical Effects on Adiposopathy Associated With the Use of GLP-1 Receptor Agonists in Chronic Kidney Disease
Associations of Early Add-On GLP-1 Receptor Agonist and SGLT2 Inhibitor Therapy With Mortality and Kidney Outcomes in Adults With Obesity and Type 2 Diabetes Across Cardiovascular-Kidney-Metabolic Stages 2-3: A Target-Trial Emulation
Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 151 citations in OpenAlex.
- Influence of glucagon-like peptide-1 receptor agonists on renal parameters: a meta-analysis of randomized controlled trials.BMC endocrine disorders · 2025Pooled it
- Comparative effects of semaglutide tirzepatide and retatrutide on renal fibrosis in UUO and aged mice.iScience · 2026Article
- A clinical and experimental investigation of liraglutide effects on the brain-kidney axis.Science advances · 2026Article
- Renal Effects of Glucagon-like Peptide-1 Receptor Agonists in Diabetic Kidney Disease: A Narrative Review of Mechanisms and Clinical Evidence.Medicina (Kaunas, Lithuania) · 2026Review
- Mechanisms of GLP-1 Receptor Agonists in HFpEF: Exploring Weight-Dependent and Independent Drivers of Therapeutic Benefit.Circulation. Heart failure · 2026Review
- Glucagon-Like Peptide-1 Receptor Agonists in Chronic Kidney Disease: Mechanisms and Clinical Perspectives.Kidney medicine · 2026Review
- Integrating GLP-1 Receptor Agonists into Modern Stroke Prevention: Evidence, Mechanisms, and Clinical Consideration-A Narrative Review.Biomedicines · 2026Review
- Molecular Mechanisms and Clinical Evidence Supporting the Four Pillars of Therapy in Diabetic Kidney Disease: Emerging Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Liraglutide and renal mitochondrial homeostasis: targeting the "metabolism-inflammation-lithogenesis" axis in metabolic syndrome.Frontiers in pharmacology · 2026Review
- Cardio-kidney-metabolic protective effects of semaglutide across the spectrum of chronic kidney disease.World journal of nephrology · 2025Review
- Idiopathic Intracranial Hypertension in Children and Adolescents with Obesity: A Narrative Review.Children (Basel, Switzerland) · 2025Review
- Current and Emerging Roles of GLP1 Receptor Agonists Across the Spectrum of Left Ventricular Ejection Fraction in Heart Failure.Biomolecules · 2025Review
- Metformin induces diarrhea in mice under over-eating conditions.Diabetology international · 2025Article
- Effects of oral antidiabetic agents on the renin-angiotensin-aldosterone system.European journal of clinical pharmacology · 2025Review
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Glucagon-like peptide-1 receptor modulates cerebrospinal fluid secretion and intracranial pressure in rats.Fluids and barriers of the CNS · 2025Article
- How to Enhance Cardiorenal Benefits in Patients With Chronic Heart Failure?International journal of heart failure · 2025Review
- Role of obesity in chronic kidney disease progression.Current research in physiology · 2025Review
- Idiopathic intracranial hypertension: Imaging and clinical fundamentals.World journal of radiology · 2024Review
- Cyclic Adenosine Monophosphate Signaling in Chronic Kidney Disease: Molecular Targets and Therapeutic Potentials.International journal of molecular sciences · 2024Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The gut incretin hormone glucagon-like peptide 1 (GLP-1) is released in response to ingested nutrients and enhances insulin secretion. In addition to its insulinotropic properties, GLP-1 has been shown to have natriuretic actions paralleled by a diminished proton secretion. We therefore studied the role of the GLP-1 receptor agonist exendin-4 in modulating the activity of Na(+)/H(+) exchanger NHE3 in LLC-PK(1) cells. We found that NHE3-mediated Na(+)-dependent intracellular pH (pH(i)) recovery decreased approximately 50% after 30-min treatment with 1 nM exendin-4. Pharmacological inhibitors and cAMP analogs that selectively activate protein kinase A (PKA) or the exchange protein directly activated by cAMP (EPAC) demonstrated that regulation of NHE3 activity by exendin-4 requires activation of both cAMP downstream effectors. This conclusion was based on the following observations: 1) the PKA antagonist H-89 completely prevented the effect of the PKA activator but only partially blocked the exendin-4-induced NHE3 inhibition; 2) the MEK1/2 inhibitor U-0126 abolished the effect of the EPAC activator but only diminished the exendin-4-induced NHE3 inhibition; 3) combination of H-89 and U-0126 fully prevented the effect of exendin-4 on NHE3; 4) no additive effect in the inhibition of NHE3 activity was observed when exendin-4, PKA, and EPAC activators were used together. Mechanistically, the inhibitory effect of exendin-4 on pH(i) recovery was associated with an increase of NHE3 phosphorylation. Conversely, this inhibition took place without changes in the surface expression of the transporter. We conclude that GLP-1 receptor agonists modulate sodium homeostasis in the kidney, most likely by affecting NHE3 activity.
Indexed as
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What OpenQuestion holds
Registered trials
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.