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 journalArticle

27 Citations (Scopus)

Abstract

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
Volume6
Issue number1
DOIs
Publication statusPublished - 2011

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Endothelial cells
nitric oxide synthase
insulin resistance
endothelial cells
Insulin Resistance
Endothelial Cells
glucosamine
Insulin
insulin
therapeutics
phosphatidylinositol 3-kinase
Nitric Oxide Synthase
hyperglycemia
Phosphodiesterase 5 Inhibitors
blood vessels
Glucosamine
quantitative polymerase chain reaction
oxidative stress
heart
glucose

ASJC Scopus subject areas

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

Cite this

Mammi, C., Pastore, D., Lombardo, M. F., Ferrelli, F., Caprio, M., Consoli, C., ... Lauro, D. (2011). Sildenafil reduces insulin-resistance in human endothelial cells. PLoS One, 6(1), [e14542]. https://doi.org/10.1371/journal.pone.0014542

Sildenafil reduces insulin-resistance in human endothelial cells. / Mammi, Caterina; Pastore, Donatella; Lombardo, Marco F.; Ferrelli, Francesca; Caprio, Massimiliano; Consoli, Claudia; Tesauro, Manfredi; Gatta, Lucia; Fini, Massimo; Federici, Massimo; Sbraccia, Paolo; Donadel, Giulia; Bellia, Alfonso; Rosano, Giuseppe M.; Fabbri, Andrea; Lauro, Davide.

In: PLoS One, Vol. 6, No. 1, e14542, 2011.

Research output: Contribution to journalArticle

Mammi, C, Pastore, D, Lombardo, MF, Ferrelli, F, Caprio, M, Consoli, C, Tesauro, M, Gatta, L, Fini, M, Federici, M, Sbraccia, P, Donadel, G, Bellia, A, Rosano, GM, Fabbri, A & Lauro, D 2011, 'Sildenafil reduces insulin-resistance in human endothelial cells', PLoS One, vol. 6, no. 1, e14542. https://doi.org/10.1371/journal.pone.0014542
Mammi, Caterina ; Pastore, Donatella ; Lombardo, Marco F. ; Ferrelli, Francesca ; Caprio, Massimiliano ; Consoli, Claudia ; Tesauro, Manfredi ; Gatta, Lucia ; Fini, Massimo ; Federici, Massimo ; Sbraccia, Paolo ; Donadel, Giulia ; Bellia, Alfonso ; Rosano, Giuseppe M. ; Fabbri, Andrea ; Lauro, Davide. / Sildenafil reduces insulin-resistance in human endothelial cells. In: PLoS One. 2011 ; Vol. 6, No. 1.
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AU - Ferrelli, Francesca

AU - Caprio, Massimiliano

AU - Consoli, Claudia

AU - Tesauro, Manfredi

AU - Gatta, Lucia

AU - Fini, Massimo

AU - Federici, Massimo

AU - Sbraccia, Paolo

AU - Donadel, Giulia

AU - Bellia, Alfonso

AU - Rosano, Giuseppe M.

AU - Fabbri, Andrea

AU - Lauro, Davide

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