ArticleCardiovascular diabetology2016
Metformin improves the angiogenic functions of endothelial progenitor cells via activating AMPK/eNOS pathway in diabetic mice.
Article in Cardiovascular diabetology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 173 citations in OpenAlex.
- Systematic review and meta-analysis of mouse models of diabetes-associated ulcers.BMJ open diabetes research & care · 2020Pooled it
- The addition of vildagliptin to metformin prevents the elevation of interleukin 1ß in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, open-label study.Cardiovascular diabetology · 2017 · on this mapTrial
- Metabolic reprogramming in diabetic panvascular disease: Molecular mechanism and therapeutic strategies.iScience · 2026Review
- Potential protective associations of antidiabetic and lipid-lowering therapies with retinal vein occlusion risk: a systematic review and meta-analysis.Eye (London, England) · 2026Review
- Single-cell insights into maladaptive endothelial plasticity and therapeutic targets in diabetic vascular complications.Cardiovascular diabetology · 2026Review
- Metformin as an Adjunct in Periodontal Therapy: Mechanistic Insights, Research Evidence and Current Challenges.Therapeutic innovation & regulatory science · 2026Review
- A multifunctional hyaluronic acid hydrogel with pH-responsive metformin release for accelerated healing of diabetic infected wounds.Materials today. Bio · 2026Article
- The Broken Cradle: Bone Marrow Stem Cell Niche Remodelling in Diabetes.Stem cell reviews and reports · 2026Review
- Metformin and butyrate attenuate chronic radiation proctitis by alleviating inflammation and macrophage senescence.Frontiers in immunology · 2026Article
- Update on the impact of lipid and glucose control on diabetic wound healing.Metabolism open · 2025Review
- Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus.World journal of stem cells · 2025Review
- The GRK2/AP-1 Signaling Axis Mediates Vascular Endothelial Dysfunction and Atherosclerosis Induced by Oscillatory Low Shear Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The ileal crypt ultrastructural changes accompanying cryptosporidiosis in type 1 diabetic mouse model versus dexamethasone-immunocompromised mouse model.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2025Article
- Polyethylene Glycol Loxenatide Accelerates Diabetic Wound Healing by Downregulating Systemic Inflammation and Improving Endothelial Progenitor Cell Functions.International journal of molecular sciences · 2025Article
- Modulation of placental angiogenesis by metformin in a rat model of gestational diabetes.Histochemistry and cell biology · 2025Article
- Innovations in hydrogel therapies for diabetic wound healing: bridging the gap between pathophysiology and clinical application.Burns & trauma · 2025Review
- Oral Active Carbon Quantum Dots for Diabetes.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Therapeutic Effects of Metformin on Central Nervous System Diseases: A Focus on Protection of Neurovascular Unit.Pharmaceutical research · 2024Review
- Impact of metformin, statin, aspirin and insulin on the prognosis of uHCC patients receiving first line Lenvatinib or Atezolizumab plus Bevacizumab.Scientific reports · 2024Article
- Gemigliptin, a potent selective dipeptidyl peptidase 4 inhibitor, protects endothelial progenitor cells by oxidative stress via caspase-3 dependent pathway.Biochemistry and biophysics reports · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEndothelial dysfunction has been suggested as a possible causal link between hyperglycemia and microvascular complications in diabetes mellitus. The effect of metformin on endothelial progenitor cells (EPCs) is still unclear. This study was designed to test the hypothesis that metformin could accelerate wound healing by improving the impaired EPC functions in streptozotocin-induced diabetic mice.
methodsStreptozotocin (STZ, 60 mg/kg/d × 5 d, i.p.) was injected to induce type 1 diabetes in male C57BL/6 mice. Mice were treated with metformin (250 mg/kg/d, i.g.) for consecutive 14 days. Wound closure was evaluated by wound area and number of CD31 stained capillaries. Functions of bone marrow-endothelial progenitor cells (BM-EPCs) were assessed by tube formation and migration assays, and expression of AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS) was determined by western blot analysis.
resultsMetformin accelerated wound closure and stimulated angiogenesis in diabetic mice. The number of circulating EPCs was increased significantly in metformin treated diabetic mice. Abilities of tube formation and migration of BM-EPCs were impaired in diabetic mice, which were improved by metformin. Expression of both phosphorylated-AMPK and phosphorylated-eNOS was significantly increased, and nitric oxide (NO) production was enhanced by metformin in BM-EPCs of diabetic mice. In vitro, metformin improved impaired BM-EPC functions, and increased phosphorylated-eNOS expression and NO production in cultured BM-EPCs caused by high glucose, which was prevented by the AMPK inhibitor compound C.
conclusionsOur results suggest that metformin could improve BM-EPC functions in STZ-induced diabetic mice, which was possibly dependent on the AMPK/eNOS pathway.
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