ArticleDiabetologia2014
Selenoprotein P as a diabetes-associated hepatokine that impairs angiogenesis by inducing VEGF resistance in vascular endothelial cells.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Selenium exposure and the risk of type 2 diabetes: a systematic review and meta-analysis.European journal of epidemiology · 2018Pooled it
- Circulating selenoprotein P levels predict glucose-lowering and insulinotropic effects of metformin, but not alogliptin: A post-hoc analysis.Journal of diabetes investigation · 2023Trial
- Effects of eicosapentaenoic acid on serum levels of selenoprotein P and organ-specific insulin sensitivity in humans with dyslipidemia and type 2 diabetes.Journal of diabetes investigation · 2022Trial
- Selenoprotein P deletion ameliorates metabolic stress-associated anxiety-like behavior in male mice.Endocrinology · 2026Article
- Advances in biomedical applications of Se-based nanozymes.Journal of nanobiotechnology · 2025Review
- TheJournal of the Endocrine Society · 2025Article
- Hyperglycemia-Suppressed SMARCA5 Disrupts Transcriptional Homeostasis to Facilitate Endothelial Dysfunction in Diabetes.Diabetes & metabolism journal · 2023Article
- Article
- Lower Plasma Selenoprotein P Levels in Regularly Exercising Young Adults.Journal of the ASEAN Federation of Endocrine Societies · 2023Article
- Glycation of Tie-2 Inhibits Angiopoietin-1 Signaling Activation and Angiopoietin-1-Induced Angiogenesis.International journal of molecular sciences · 2022Article
- Article
- Selenium, a Micronutrient That Modulates Cardiovascular Health via Redox Enzymology.Nutrients · 2021Review
- Alcohol Intake Is Associated With Elevated Serum Levels of Selenium and Selenoprotein P in Humans.Frontiers in nutrition · 2021Article
- Hepatokine Selenoprotein P-Mediated Reductive Stress Causes Resistance to Intracellular Signal Transduction.Antioxidants & redox signaling · 2020Review
- Higher Serum Selenoprotein P Level as a Novel Inductor of Metabolic Complications in Psoriasis.International journal of molecular sciences · 2020Article
- Selenoprotein P as anJournal of clinical biochemistry and nutrition · 2020Review
- Serum selenoprotein P, but not selenium, predicts future hyperglycemia in a general Japanese population.Scientific reports · 2018Article
- Pathophysiological significance of hepatokine overproduction in type 2 diabetes.Diabetology international · 2018Article
- Endogenous Selenoprotein P, a Liver-Derived Secretory Protein, Mediates Myocardial Ischemia/Reperfusion Injury in Mice.International journal of molecular sciences · 2018Article
- Vascular Oxidative Stress: Impact and Therapeutic Approaches.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
24 authors at 6 institutions in 1 country.
Funding
Abstract
aims/hypothesisImpaired angiogenesis induced by vascular endothelial growth factor (VEGF) resistance is a hallmark of vascular complications in type 2 diabetes; however, its molecular mechanism is not fully understood. We have previously identified selenoprotein P (SeP, encoded by the SEPP1 gene in humans) as a liver-derived secretory protein that induces insulin resistance. Levels of serum SeP and hepatic expression of SEPP1 are elevated in type 2 diabetes. Here, we investigated the effects of SeP on VEGF signalling and angiogenesis.
methodsWe assessed the action of glucose on Sepp1 expression in cultured hepatocytes. We examined the actions of SeP on VEGF signalling and VEGF-induced angiogenesis in HUVECs. We assessed wound healing in mice with hepatic SeP overexpression or SeP deletion. The blood flow recovery after ischaemia was also examined by using hindlimb ischaemia model with Sepp1-heterozygous-knockout mice.
resultsTreatment with glucose increased gene expression and transcriptional activity for Sepp1 in H4IIEC hepatocytes. Physiological concentrations of SeP inhibited VEGF-stimulated cell proliferation, tubule formation and migration in HUVECs. SeP suppressed VEGF-induced reactive oxygen species (ROS) generation and phosphorylation of VEGF receptor 2 (VEGFR2) and extracellular signal-regulated kinase 1/2 (ERK1/2) in HUVECs. Wound closure was impaired in the mice overexpressing Sepp1, whereas it was improved in SeP (-/-)mice. SeP (+/-)mice showed an increase in blood flow recovery and vascular endothelial cells after hindlimb ischaemia. CONCLUSIONS/
interpretationThe hepatokine SeP may be a novel therapeutic target for impaired angiogenesis in type 2 diabetes.
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