ArticleActa pharmacologica Sinica2023
SGLT2 inhibitor empagliflozin promotes revascularization in diabetic mouse hindlimb ischemia by inhibiting ferroptosis.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- SGLT2 Inhibitors Promote Diabetic Wound Healing Via AMPK/AKT/mTORC1-Regulated Endothelial Angiogenesis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- From molecules to the clinic-pathophysiology of sodium-glucose cotransporter 2 inhibitors and their emerging role in urology: A comprehensive review from the European Association of Urology Section of Endourology.Asian journal of urology · 2026Review
- Umbilical cord mesenchymal stem cells and their extracellular vesicles attenuate cryopreservation-induced ovarian injury via the suppression of ferroptosis in an in vitro culture system.Materials today. Bio · 2026Article
- Role and mechanisms of vascular smooth muscle cell phenotypic transition in diabetic macrovascular complications.Biological research · 2026Review
- Glucolipid metabolic disorders and ferroptosis in diabetic ulcers: pathogenic crossroads and therapeutic opportunities.Frontiers in endocrinology · 2026Review
- Sodium-glucose cotransporter 2 inhibitors ameliorate glutathione cysteine ligase modifier-mediated oxidative stress and subsequent ferroptosis in proximal tubules of diabetic kidney disease.Redox report : communications in free radical research · 2025Article
- Dapagliflozin improves diabetic kidney disease by inhibiting ferroptosis through β-hydroxybutyrate production.Renal failure · 2025Article
- Comparative evaluation of ferroptosis markers NCOA4, ACSL4, and Nrf2 in periodontitis with and without type 2 diabetes mellitus: a case-control study.Clinical oral investigations · 2025Article
- Crosstalk between ferroptosis and miRNA in type 2 diabetes mellitus and possible therapeutic targeting.European journal of medical research · 2025Review
- Sodium-glucose cotransporter 2 inhibitors and atherosclerosis.American journal of preventive cardiology · 2025Review
- Pathophysiological Mechanisms of Diabetes-Induced Macrovascular and Microvascular Complications: The Role of Oxidative Stress.Medical sciences (Basel, Switzerland) · 2025Review
- Endothelial dysfunction in chronic kidney disease: a clinical perspective.American journal of physiology. Heart and circulatory physiology · 2025Review
- Exploring the Protective Effects of Traditional Antidiabetic Medications and Novel Antihyperglycemic Agents in Diabetic Rodent Models.Pharmaceuticals (Basel, Switzerland) · 2025Review
- p52-ZER6/DAZAP1 axis promotes ferroptosis resistance and colorectal cancer progressionActa pharmaceutica Sinica. B · 2025Article
- Advances in Ferroptosis Research: A Comprehensive Review of Mechanism Exploration, Drug Development, and Disease Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Empagliflozin-Pretreated MSC-Derived Exosomes Enhance Angiogenesis and Wound Healing via PTEN/AKT/VEGF Pathway.International journal of nanomedicine · 2025Article
- From bench to bedside: targeting ferroptosis and mitochondrial damage in the treatment of diabetic cardiomyopathy.Frontiers in endocrinology · 2025Review
- Targeting ion channel networks in diabetic kidney disease: from molecular crosstalk to precision therapeutics and clinical innovation.Frontiers in medicine · 2025Review
- Aging promotes metabolic dysfunction-associated steatotic liver disease by inducing ferroptotic stress.Nature aging · 2024Article
- Effect of dapagliflozin on ferroptosis through the gut microbiota metabolite TMAO during myocardial ischemia-reperfusion injury in diabetes mellitus rats.Scientific reports · 2024Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gliflozins are known as SGLT2 inhibitors, which are used to treat diabetic patients by inhibiting glucose reabsorption in kidney proximal tubules. Recent studies show that gliflozins may exert other effects independent of SGLT2 pathways. In this study we investigated their effects on skeletal muscle cell viability and paracrine function, which were crucial for promoting revascularization in diabetic hindlimb ischemia (HLI). We showed that treatment with empagliflozin (0.1-40 μM) dose-dependently increased high glucose (25 mM)-impaired viability of skeletal muscle C2C12 cells. Canagliflozin, dapagliflozin, ertugliflozin, ipragliflozin and tofogliflozin exerted similar protective effects on skeletal muscle cells cultured under the hyperglycemic condition. Transcriptomic analysis revealed an enrichment of pathways related to ferroptosis in empagliflozin-treated C2C12 cells. We further demonstrated that empagliflozin and other gliflozins (10 μM) restored GPX4 expression in high glucose-treated C2C12 cells, thereby suppressing ferroptosis and promoting cell viability. Empagliflozin (10 μM) also markedly enhanced the proliferation and migration of blood vessel-forming cells by promoting paracrine function of skeletal muscle C2C12 cells. In diabetic HLI mice, injection of empagliflozin into the gastrocnemius muscle of the left hindlimb (10 mg/kg, every 3 days for 21 days) significantly enhanced revascularization and blood perfusion recovery. Collectively, these results reveal a novel effect of empagliflozin, a clinical hypoglycemic gliflozin drug, in inhibiting ferroptosis and enhancing skeletal muscle cell survival and paracrine function under hyperglycemic condition via restoring the expression of GPX4. This study highlights the potential of intramuscular injection of empagliflozin for treating diabetic HLI.
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