ArticleCardiovascular research2019
Cardiac sodium-dependent glucose cotransporter 1 is a novel mediator of ischaemia/reperfusion injury.
Article in Cardiovascular research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis.Scientific reports · 2024Pooled it
- Sodium-glucose cotransporter 2 inhibitors reduce myocardial infarct size in preclinical animal models of myocardial ischaemia-reperfusion injury: a meta-analysis.Diabetologia · 2021Pooled it
- SGLT2 inhibition improves sarcomere contractile dysfunction in human models of dilated cardiomyopathy.Journal of translational medicine · 2026Article
- Hospitalization, ICU admission, and mortality among diabetic patients with inflammatory bowel disease receiving SGLT-2 inhibitors: a retrospective cohort study from the global collaborative network.Annals of translational medicine · 2026Article
- Sotagliflozin Enhances Left Ventricular Function and Myocardial Perfusion in Chronic Myocardial Ischemia Through Metabolic and Redox Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Cardiac sodium-glucose co-transporter 1 (SGLT1) contributes to heart failure in a mouse model of diabetic cardiomyopathy.Basic research in cardiology · 2025Article
- Astragaloside IV protects against high altitude hypoxia-induced cardiac injury through the CaSR-NF-kB and EGFR-PI3K-AKT-MDM2 pathways.Apoptosis : an international journal on programmed cell death · 2025Article
- Cardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia.Cardiovascular diabetology · 2025Article
- Targeting Lactic Acid Modification in Ischemic Heart Diseases: Novel Therapeutics and Mechanism.Journal of cardiovascular translational research · 2025Review
- Different starch sources and amino acid levels on growth performance, starch and amino acids digestion, absorption and metabolism of 0- to 3-week-old broilers fed low protein diet.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- The real-world anti-inflammatory effect of SGLT2i in patients with chronic heart failure.Journal of medicine and life · 2025Article
- Comparative cardiovascular risks of canagliflozin and selective SGLT2 inhibitors in type 2 diabetes.Frontiers in pharmacology · 2025Article
- Protective Mechanisms of SGLTi in Ischemic Heart Disease.Journal of cardiovascular translational research · 2024Review
- Advances in the Insulin-Heart Axis: Current Therapies and Future Directions.International journal of molecular sciences · 2024Review
- The Off-Target Cardioprotective Mechanisms of Sodium-Glucose Cotransporter 2 Inhibitors: An Overview.International journal of molecular sciences · 2024Review
- Sodium-glucose cotransporter 1 promotes the biofunctions of perivascular preadipocytes mediated by Akt/mTOR/p70S6K signaling pathway.American journal of physiology. Cell physiology · 2024Article
- Guideline-Optimised Treatment in Heart Failure-Do Higher Doses Reduce Systemic Inflammation More Significantly?Journal of clinical medicine · 2024Article
- Article
- SGLT2 inhibitors: Beyond glycemic control.Journal of clinical & translational endocrinology · 2024Article
- SGLT2 inhibitors for alleviating heart failure through non-hypoglycemic mechanisms.Frontiers in cardiovascular medicine · 2024Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
aimsWe previously reported that sodium-dependent glucose cotransporter 1 (SGLT1) is highly expressed in cardiomyocytes and is further up-regulated in ischaemia. This study aimed to determine the mechanisms by which SGLT1 contributes to ischaemia/reperfusion (I/R) injury. METHODS AND
resultsMice with cardiomyocyte-specific knockdown of SGLT1 (TGSGLT1-DOWN) and wild-type controls were studied. In vivo, the left anterior descending coronary artery was ligated for 30 min and reperfused for 48 h. Ex vivo, isolated perfused hearts were exposed to 20 min no-flow and up to 2 h reperfusion. In vitro, HL-1 cells and isolated adult murine ventricular cardiomyocytes were exposed to 1 h hypoxia and 24 h reoxygenation (H/R). We found that TGSGLT1-DOWN hearts were protected from I/R injury in vivo and ex vivo, with decreased infarct size, necrosis, dysfunction, and oxidative stress. 5'-AMP-activated protein kinase (AMPK) activation increased SGLT1 expression, which was abolished by extracellular signal-related kinase (ERK) inhibition. Co-immunoprecipitation studies showed that ERK, but not AMPK, interacts directly with SGLT1. AMPK activation increased binding of the hepatocyte nuclear factor 1 and specificity protein 1 transcription factors to the SGLT1 gene, and HuR to SGLT1 mRNA. In cells, up-regulation of SGLT1 during H/R was abrogated by AMPK inhibition. Co-immunoprecipitation studies showed that SGLT1 interacts with epidermal growth factor receptor (EGFR), and EGFR interacts with protein kinase C (PKC). SGLT1 overexpression activated PKC and NADPH oxidase 2 (Nox2), which was attenuated by PKC inhibition, EGFR inhibition, and/or disruption of the interaction between EGFR and SGLT1.
conclusionDuring ischaemia, AMPK up-regulates SGLT1 through ERK, and SGLT1 interacts with EGFR, which in turn increases PKC and Nox2 activity and oxidative stress. SGLT1 may represent a novel therapeutic target for mitigating I/R injury.
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