ArticleJournal of the American Heart Association2015
Intracellular Na+ Concentration ([Na+]i) Is Elevated in Diabetic Hearts Due to Enhanced Na+-Glucose Cotransport.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Network and Pairwise Meta-Analysis of the Association Between Novel Hypoglycemic Agents and Atrial Fibrillation Risk in Patients With Type 2 Diabetes Mellitus.Diabetes/metabolism research and reviews · 2026Pooled it
- Dual inhibition of SGLT 1 and 2 by sotagliflozin alleviates intracellular sodium overload and improves cardiometabolic remodelling in uraemic cardiomyopathy.Cardiovascular research · 2026Article
- Dual SGLT1/2 inhibition with sotagliflozin improves cardiac function and metabolism in type 2 diabetic mice.npj metabolic health and disease · 2026Article
- Cardiac remodelling in type 2 diabetes: Pathophysiological mechanisms and opportunities for multiscale computational modelling and simulation.The Journal of physiology · 2026Review
- Sodium-myo-inositol cotransporter-1, SMIT1, promotes cardiac hypertrophy and fibrosis induced by pressure overload in mice.Cardiovascular research · 2026Article
- Cardiac sodium-glucose co-transporter 1 (SGLT1) contributes to heart failure in a mouse model of diabetic cardiomyopathy.Basic research in cardiology · 2025Article
- Calcium Signaling and Cardiac Adaptation to Stress: Focus on Pregnancy and Diabetes.Biomolecules · 2025Review
- A primer on copper biology in the brain.Neurobiology of disease · 2025Review
- Type 2 diabetes worsens the outcome of ischemia/reperfusion in female STEMI patients and female db/db mice with HFpEF cardiometabolic phenotype.Cardiovascular diabetology · 2025Article
- Sodium-glucose exchanger 2 inhibitor canagliflozin promotes mitochondrial metabolism and alleviates salt-induced cardiac hypertrophy via preserving SIRT3 expression.Journal of advanced research · 2025Article
- Empagliflozin in diabetic cardiomyopathy: elucidating mechanisms, therapeutic potentials, and future directions.Molecular biology reports · 2025Review
- The Role of Sodium Glucose Co-Transporter 2 Inhibitors in Atrial Fibrillation: A Comprehensive Review.Journal of clinical medicine · 2024Review
- Roles of non-coding RNA in diabetic cardiomyopathy.Cardiovascular diabetology · 2024Review
- Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Anti-Inflammation and Anti-Oxidation: The Key to Unlocking the Cardiovascular Potential of SGLT2 Inhibitors and GLP1 Receptor Agonists.Antioxidants (Basel, Switzerland) · 2023Review
- The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress-Role of New Drugs, Flozins.Biomedicines · 2023Review
- Distinct Effects of Mitochondrial NaJournal of the American Heart Association · 2023Article
- SGLT2 inhibitor ertugliflozin decreases elevated intracellular sodium, and improves energetics and contractile function in diabetic cardiomyopathy.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023Review
- Use of sodium-glucose cotransporter-2 inhibitors and the risk for sudden cardiac arrest and for all-cause death in patients with type 2 diabetes mellitus.European heart journal. Cardiovascular pharmacotherapy · 2022Article
7 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntracellular Na(+) concentration ([Na(+)]i) regulates Ca(2+) cycling, contractility, metabolism, and electrical stability of the heart. [Na(+)]i is elevated in heart failure, leading to arrhythmias and oxidative stress. We hypothesized that myocyte [Na(+)]i is also increased in type 2 diabetes (T2D) due to enhanced activity of the Na(+)-glucose cotransporter. METHODS AND
resultsTo test this hypothesis, we used myocardial tissue from humans with T2D and a rat model of late-onset T2D (HIP rat). Western blot analysis showed increased Na(+)-glucose cotransporter expression in failing hearts from T2D patients compared with nondiabetic persons (by 73±13%) and in HIP rat hearts versus wild-type (WT) littermates (by 61±8%). [Na(+)]i was elevated in HIP rat myocytes both at rest (14.7±0.9 versus 11.4±0.7 mmol/L in WT) and during electrical stimulation (17.3±0.8 versus 15.0±0.7 mmol/L); however, the Na(+)/K(+)-pump function was similar in HIP and WT cells, suggesting that higher [Na(+)]i is due to enhanced Na(+) entry in diabetic hearts. Indeed, Na(+) influx was significantly larger in myocytes from HIP versus WT rats (1.77±0.11 versus 1.29±0.06 mmol/L per minute). Na(+)-glucose cotransporter inhibition with phlorizin or glucose-free solution greatly reduced Na(+) influx in HIP myocytes (to 1.20±0.16 mmol/L per minute), whereas it had no effect in WT cells. Phlorizin also significantly decreased glucose uptake in HIP myocytes (by 33±9%) but not in WT, indicating an increased reliance on the Na(+)-glucose cotransporter for glucose uptake in T2D hearts.
conclusionsMyocyte Na(+)-glucose cotransport is enhanced in T2D, which increases Na(+) influx and causes Na(+) overload. Higher [Na(+)]i may contribute to arrhythmogenesis and oxidative stress in diabetic hearts.
Indexed as
Identifiers
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.