ArticleScientific reports2016
Dipeptidyl Peptidase-4 Inhibitor Increases Vascular Leakage in Retina through VE-cadherin Phosphorylation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Association between dipeptidyl peptidase-4 inhibitor use and diabetic retinopathy: a systematic review and meta-analysis of real-world studies.BMC ophthalmology · 2024Pooled it
- Associations of antidiabetic drugs with diabetic retinopathy in people with type 2 diabetes: an umbrella review and meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Neurovascular Actions of Dipeptidyl Peptidase-4 Inhibitors and Their Implications for Cognitive Dysfunction in Type 2 Diabetes Mellitus.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Review
- Disrupting VE-cadherin Y685 phosphorylation inhibits development of experimental diabetic and prediabetic retinopathy.The Journal of clinical investigation · 2026Article
- Association of long-term use of dipeptidyl peptidase-4 inhibitors with the risk of diabetic retinopathy in patients with diabetes mellitus: a real-world evidence study.Frontiers in pharmacology · 2025Article
- Incretin-based therapy: a new horizon in diabetes management.Journal of diabetes and metabolic disorders · 2024Review
- The association between uncontrolled hyperglycemia (Type-2 Diabetes) and cardiovascular sequelae in patients with and without insulin.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
- Comparative Effectiveness of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter 2 Inhibitors, Dipeptidyl Peptidase-4 Inhibitors, and Sulfonylureas for Sight-Threatening Diabetic Retinopathy.Ophthalmology. Retina · 2024Observational
- Lower Atrial Fibrillation Risk With Sodium-Glucose Cotransporter 2 Inhibitors Than With Dipeptidyl Peptidase-4 Inhibitors in Individuals With Type 2 Diabetes: A Nationwide Cohort Study.Korean circulation journal · 2024Article
- Novel Antidiabetic Drugs and the Risk of Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Journal of clinical medicine · 2024Review
- Genome-wide association identifies novel ROP risk loci in a multiethnic cohort.Communications biology · 2024Article
- Long-term increase in fasting blood glucose is associated with increased risk of sudden cardiac arrest.Cardiovascular diabetology · 2023Article
- Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy.International journal of molecular sciences · 2023Article
- Does DPP-IV Inhibition Offer New Avenues for Therapeutic Intervention in Malignant Disease?Cancers · 2022Review
- Article
- Diprotin A TFA Exerts Neurovascular Protection in Ischemic Cerebral Stroke.Frontiers in neuroscience · 2022Article
- HIV-1 Tat and Heparan Sulfate Proteoglycans Orchestrate the Setup ofMolecules (Basel, Switzerland) · 2021Article
- Association between Add-On Dipeptidyl Peptidase-4 Inhibitor Therapy and Diabetic Retinopathy Progression.Journal of clinical medicine · 2021Article
- Dihydrotanshinone, a Natural Diterpenoid, Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor.International journal of molecular sciences · 2020Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibitors of CD26 (dipeptidyl peptidase-4; DPP4) have been widely prescribed to control glucose level in diabetic patients. DPP4-inhibitors, however, accumulate stromal cell-derived factor-1α (SDF-1α), a well-known inducer of vascular leakage and angiogenesis both of which are fundamental pathophysiology of diabetic retinopathy. The aim of this study was to investigate the effects of DPP4-inhibitors on vascular permeability and diabetic retinopathy. DPP4-inhibitor (diprotin A or sitagliptin) increased the phosphorylation of Src and vascular endothelial-cadherin (VE-cadherin) in human endothelial cells and disrupted endothelial cell-to-cell junctions, which were attenuated by CXCR4 (receptor of SDF-1α)-blocker or Src-inhibitor. Disruption of endothelial cell-to-cell junctions in the immuno-fluorescence images correlated with the actual leakage of the endothelial monolayer in the transwell endothelial permeability assay. In the Miles assay, vascular leakage was observed in the ears into which SDF-1α was injected, and this effect was aggravated by DPP4-inhibitor. In the model of retinopathy of prematurity, DPP4-inhibitor increased not only retinal vascularity but also leakage. Additionally, in the murine diabetic retinopathy model, DPP4-inhibitor increased the phosphorylation of Src and VE-cadherin and aggravated vascular leakage in the retinas. Collectively, DPP4-inhibitor induced vascular leakage by augmenting the SDF-1α/CXCR4/Src/VE-cadherin signaling pathway. These data highlight safety issues associated with the use of DPP4-inhibitors.
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Registered trials
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