Sildenafil reduces insulin-resistance in human endothelial cells

Caterina Mammi, Donatella Pastore, Marco F. Lombardo, Francesca Ferrelli, Massimiliano Caprio, Claudia Consoli, Manfredi Tesauro, Lucia Gatta, Massimo Fini, Massimo Federici, Paolo Sbraccia, Giulia Donadel, Alfonso Bellia, Giuseppe M. Rosano, Andrea Fabbri, Davide Lauro

Research output: Contribution to journalArticlepeer-review


Background: The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro. Methodology/Principal Findings: Human umbilical vein endothelial cells (HUVECs) were treated with insulin in presence of glucose 30 mM (HG) and glucosamine 10 mM (Gluc-N) with or without sildenafil. Insulin increased the expression of PDE5 and eNOS mRNA assayed by Real time-PCR. Cytofluorimetric analysis showed that sildenafil significantly increased NO production in basal condition. This effect was partially inhibited by the PI3K inhibitor LY 294002 and completely inhibited by the NOS inhibitor L-NAME. Akt-1 and eNOS activation was reduced in conditions mimicking insulin resistance and completely restored by sildenafil treatment. Conversely sildenafil treatment can counteract this noxious effect by increasing NO production through eNOS activation and reducing oxidative stress induced by hyperglycaemia and glucosamine. Conclusions/Significance: These data indicate that sildenafil might improve NOS activity of endothelial cells in insulin resistance conditions and suggest the potential therapeutic use of sildenafil for improving vascular function in diabetic patients.

Original languageEnglish
Article numbere14542
JournalPLoS One
Issue number1
Publication statusPublished - 2011

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


Dive into the research topics of 'Sildenafil reduces insulin-resistance in human endothelial cells'. Together they form a unique fingerprint.

Cite this