ArticleAmerican journal of physiology. Renal physiology2007
Characterization of the regulation of renal Na+/H+ exchanger NHE3 by insulin.
Article in American journal of physiology. Renal physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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Who cites it
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- The Genetic Associations Between Kidney Stones, Obesity, Type 2 Diabetes, and Hypertension.Mayo Clinic proceedings · 2025Pooled it
- The effect of single nucleotide polymorphisms on depression in combination with coronary diseases: a systematic review and meta-analysis.Frontiers in endocrinology · 2024Pooled it
- Increased production and reduced urinary buffering of acid in uric acid stone formers is ameliorated by pioglitazone.Kidney international · 2019Trial
- Composite metabolic indices and calcium oxalate stone formation: a multicenter comparative study of HOMA-IR, PAI, TyG, and METS-IR.International urology and nephrology · 2026Article
- Receptor-mediated endocytosis by Megalin: Exploring its role in ligand interaction and disease mechanisms.Genes & diseases · 2026Review
- Na/K-ATPase in the renal proximal tubule cell: classic & novel roles in sodium handling.Frontiers in physiology · 2026Review
- High Estimated 24-Hour Urinary Sodium Excretion is Associated With Metabolic Syndrome and Its Phenotypes: Tehran Lipid and Glucose Study.Journal of nutrition and metabolism · 2026Article
- Association of insulin resistance indices with kidney stones and their recurrence in a non-diabetic population: an analysis based on NHANES data from 2007-2018.Renal failure · 2025Article
- High-Fructose-Induced Salt-Sensitive Hypertension: The Potential Benefit of SGLT4 or SGLT5 Modulation.Nutrients · 2025Review
- Inverted V-shaped association between atherogenic index of plasma and kidney stone risk: results from NHANES 2011-2018.Translational andrology and urology · 2025Article
- Association between insulin resistance indices and kidney stones: results from the 2015-2018 National Health and Nutrition Examination Survey.Frontiers in nutrition · 2024Article
- Insulin augments angiotensin II-induced myocardial fibrosis via the MEK/STAT3 pathway.Heliyon · 2023Article
- Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control.Biomedicines · 2023Review
- Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades.Antibiotics (Basel, Switzerland) · 2023Article
- Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt.International journal of molecular sciences · 2023Review
- The Post-Translational Modification Networking in WNK-Centric Hypertension Regulation and Electrolyte Homeostasis.Biomedicines · 2022Review
- Angiotensin II and ATInternational journal of molecular sciences · 2022Review
- Metformin: Expanding the Scope of Application-Starting Earlier than Yesterday, Canceling Later.International journal of molecular sciences · 2022Review
- The NaFrontiers in physiology · 2022Review
- Crosstalk between Sodium-Glucose Cotransporter Inhibitors and Sodium-Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin receptors are widely distributed in the kidney and affect multiple aspects of renal function. In the proximal tubule, insulin regulates volume and acid-base regulation through stimulation of the Na(+)/H(+) exchanger NHE3. This paper characterizes the signaling pathway by which insulin stimulates NHE3 in a cell culture model [opossum kidney (OK) cell]. Insulin has two distinct phases of action on NHE3. Chronic insulin (24 h) activates NHE3 through the classic phosphatidylinositol 3-kinase-serum- and glucocorticoid-dependent kinase 1 (PI3K-SGK1) pathway as insulin stimulates SGK1 phosphorylation and the insulin effect can be blocked by the PI3K inhibitor wortmannin or a dominant-negative SGK1. We showed that SGK1 transcript and protein are expressed in rat proximal tubule and OK cells. We previously showed that glucocorticoids augment the effect of insulin on NHE3 (Klisic J, Hu MC, Nief V, Reyes L, Fuster D, Moe OW, Ambuhl PM. Am J Physiol Renal Physiol 283: F532-F539, 2002). Part of this can be mediated via induction of SGK1 by glucocorticoids, and indeed the insulin effect on NHE3 can also be amplified by overexpression of SGK1. We next addressed the acute effect of insulin (1-2 h) on NHE3 by systematically examining the candidate signaling cascades and activation mechanisms of NHE3. We ruled out the PI3K-SGK1-Akt and TC10 pathways, increased surface NHE3, NHE3 phosphorylation, NHE3 association with calcineurin homologous protein 1 or megalin as mechanisms of acute activation of NHE3 by insulin. In summary, insulin stimulates NHE3 acutely via yet undefined pathways and mechanisms. The chronic effect of insulin is mediated by the classic PI3K-SGK1 route.
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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.