Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells
| العنوان: | Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells |
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| المؤلفون: | Massimiliano Caprio, Caterina Mammi, Manfredi Tesauro, Donatella Pastore, Marco F. Lombardo, Alfonso Bellia, Massimo Fini, Andrea Fabbri, Giuseppe M.C. Rosano, Paolo Sbraccia, Davide Lauro, Francesca Ferrelli, Giulia Donadel, Claudia Consoli, Massimo Federici, Lucia Gatta |
| المصدر: | PLoS ONE PLoS ONE, Vol 6, Iss 1, p e14542 (2011) |
| بيانات النشر: | Public Library of Science, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Settore MED/09 - Medicina Interna, medicine.medical_treatment, Vasodilator Agents, Messenger, Cardiovascular Disorders/Coronary Artery Disease, lcsh:Medicine, Settore MED/11 - Malattie dell'Apparato Cardiovascolare, Piperazines, Settore MED/13 - Endocrinologia, chemistry.chemical_compound, Insulin, Sulfones, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, lcsh:Science, Cells, Cultured, Multidisciplinary, Cultured, Settore M-EDF/01 - Metodi e Didattiche delle Attivita' Motorie, biology, Nitric Oxide Synthase Type III, PDE5 drug design, Nitric oxide synthase, Diabetes and Endocrinology, Type 5, cGMP-specific phosphodiesterase type 5, cardiovascular system, Research Article, Cyclic Nucleotide Phosphodiesterases, medicine.medical_specialty, Sildenafil, Cells, Settore MED/50 - Scienze Tecniche Mediche Applicate, Sildenafil Citrate, Nitric oxide, Insulin resistance, Internal medicine, Vascular, medicine, Humans, Endothelium, Diabetes and Endocrinology/Type 2 Diabetes, RNA, Messenger, Phosphodiesterase 5 Inhibitors, Purines, Endothelial Cells, Cyclic Nucleotide Phosphodiesterases, Type 5, Endothelium, Vascular, Insulin Resistance, Settore MED/04 - Patologia Generale, business.industry, lcsh:R, medicine.disease, respiratory tract diseases, Endocrinology, chemistry, biology.protein, RNA, lcsh:Q, business |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dfffedc3efe16c29513951348527ca14 http://europepmc.org/articles/PMC3030559 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dfffedc3efe16c29513951348527ca14 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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