ArticleJournal of the American Society of Nephrology : JASN2014
Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.
- Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.Frontiers in immunology · 2023Pooled it
- Pulmonary congestion relief by adding dapagliflozin to intravenous loop diuretic in acute heart failure patients.ESC heart failure · 2025Trial
- Effect of empagliflozin on circulating proteomics in heart failure: mechanistic insights into the EMPEROR programme.European heart journal · 2022Trial
- Renal effects of a sodium-glucose cotransporter 2 inhibitor, tofogliflozin, in relation to sodium intake and glycaemic status.Diabetes, obesity & metabolism · 2019Trial
- SGLT2 inhibitors preserve serum chloride in non-diabetic CKD: a propensity-matched and LASSO regression analysis.Renal failure · 2026Article
- Urine Recirculation During Normothermic Kidney Preservation Improves Energy Balance Involving the Urea and Citric Acid Cycles.Transplantation direct · 2026Article
- SGLT2 inhibitors for kidney protection in children: expanding horizons beyond endocrinology.Pediatric nephrology (Berlin, Germany) · 2026Review
- Cystinosin regulates NaEMBO reports · 2026Article
- Sodium-glucose cotransporter-2 inhibitor use in type 2 diabetes mellitus is associated with a lower rate of atrial arrhythmias in a hospitalized real-world population.Heart rhythm O2 · 2025Article
- Cystinosin is involved in NabioRxiv : the preprint server for biology · 2025Article
- Sodium-glucose co-transporter 2 inhibitors: a pleiotropic drug in humans with promising results in cats.Frontiers in veterinary science · 2025Review
- Factors that influence the Na/K-ATPase signaling and function.Frontiers in pharmacology · 2025Review
- Crucial role for sensory nerves and Na/H exchanger inhibition in dapagliflozin- and empagliflozin-induced arterial relaxation.Cardiovascular research · 2024Article
- SGLT2 Inhibitors and How They Work Beyond the Glucosuric Effect. State of the Art.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Review
- Modern Challenges in Type 2 Diabetes: Balancing New Medications with Multifactorial Care.Biomedicines · 2024Review
- The potential anti-arrhythmic effect of SGLT2 inhibitors.Cardiovascular diabetology · 2024Review
- Renal handling of albumin in rats with early stage diabetes: A theoretical analysis.The Journal of physiology · 2024Article
- Renal upregulation of NCC counteracts empagliflozin-mediated NHE3 inhibition in normotensive but not in hypertensive male rat.American journal of physiology. Cell physiology · 2024Article
- SGLT2-independent effects of canagliflozin on NHE3 and mitochondrial complex I activity inhibit proximal tubule fluid transport and albumin uptake.American journal of physiology. Renal physiology · 2024Article
- Ketoacidosis and SGLT2 Inhibitors: A Narrative Review.Metabolites · 2024Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Na(+)-glucose cotransporter 1 (SGLT1)-mediated glucose uptake leads to activation of Na(+)-H(+) exchanger 3 (NHE3) in the intestine by a process that is not dependent on glucose metabolism. This coactivation may be important for postprandial nutrient uptake. However, it remains to be determined whether SGLT-mediated glucose uptake regulates NHE3-mediated NaHCO3 reabsorption in the renal proximal tubule. Considering that this nephron segment also expresses SGLT2 and that the kidneys and intestine show significant variations in daily glucose availability, the goal of this study was to determine the effect of SGLT-mediated glucose uptake on NHE3 activity in the renal proximal tubule. Stationary in vivo microperfusion experiments showed that luminal perfusion with 5 mM glucose stimulates NHE3-mediated bicarbonate reabsorption. This stimulatory effect was mediated by glycolytic metabolism but not through ATP production. Conversely, luminal perfusion with 40 mM glucose inhibited NHE3 because of cell swelling. Notably, pharmacologic inhibition of SGLT activity by Phlorizin produced a marked inhibition of NHE3, even in the absence of glucose. Furthermore, immunofluorescence experiments showed that NHE3 colocalizes with SGLT2 but not SGLT1 in the rat renal proximal tubule. Collectively, these findings show that glucose exerts a bimodal effect on NHE3. The physiologic metabolism of glucose stimulates NHE3 transport activity, whereas, supraphysiologic glucose concentrations inhibit this exchanger. Additionally, Phlorizin-sensitive SGLT transporters and NHE3 interact functionally in the proximal tubule.
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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.