Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion

Detalhes bibliográficos
Autor(a) principal: Natali, A.
Data de Publicação: 2013
Outros Autores: Ribeiro, R., Baldi, S., Tulipani, A., Rossi, M., Venturi, E., Mari, A., Macedo, M. P., Ferrannini, E.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/174097
Resumo: Funding Information: Source of funding The study received partial support from FTC (Fundação para a Ciência e a Tecnologia - Portuguese Foundation for Science and Technology) under the project PTDC/DTP-EPI/0207/2012. Other funds came from resources made available by other funded studies.
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spelling Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretionInsulin clearanceInsulin secretionInsulin sensitivityNitric oxideInternal MedicineEndocrinology, Diabetes and MetabolismSDG 3 - Good Health and Well-beingFunding Information: Source of funding The study received partial support from FTC (Fundação para a Ciência e a Tecnologia - Portuguese Foundation for Science and Technology) under the project PTDC/DTP-EPI/0207/2012. Other funds came from resources made available by other funded studies.Aims/hypothesis: Endogenous NO inhibits insulin release in isolated beta cells and insulin-degrading enzyme activity in hepatocytes, while NO release from endothelial cells has been suggested to enhance insulin action. We assessed the overall effect of systemic inhibition of endogenous NO synthesis on glucose homeostasis in humans. Methods: Twenty-four non-diabetic volunteers underwent two hyperglycaemic (+7 mmol/l) clamps with either saline or L-NG-nitroarginine methyl ester (l-NAME, at rates of 2.5, 5, 10 and 20 μg min-1 kg-1) infusion. Another five volunteers underwent an OGTT with either saline or l-NAME (20 μg min-1 kg-1) infusion. Blood pressure and heart rate were measured to monitor NO blockade; during the OGTT, endothelial function was assessed by peripheral arterial tonometry and insulin secretion by C-peptide deconvolution and insulin secretion modelling. Results: Compared with saline, l-NAME at the highest dose raised mean blood pressure (+20 ± 2 mmHg), depressed heart rate (-12 ± 2 bpm) and increased insulin clearance (+50%). First-phase insulin secretion was impaired, but insulin sensitivity (M/I index) was unchanged. During the OGTT, l-NAME raised 2 h plasma glucose by 1.8 mmol/l (p < 0.01), doubled insulin clearance and impaired beta cell glucose sensitivity while depressing endothelial function. Conclusions/interpretation: In humans, systemic NO blockade titrated to increase blood pressure and induce endothelial dysfunction does not affect insulin action but significantly impairs glucose tolerance by increasing plasma insulin clearance and depressing insulin secretion, namely first-phase and beta cell glucose sensitivity.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNNatali, A.Ribeiro, R.Baldi, S.Tulipani, A.Rossi, M.Venturi, E.Mari, A.Macedo, M. P.Ferrannini, E.2024-10-26T01:22:09Z2013-052013-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://hdl.handle.net/10362/174097eng0012-186XPURE: 101917900https://doi.org/10.1007/s00125-013-2836-xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-11-11T01:39:13Zoai:run.unl.pt:10362/174097Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-11T01:39:13Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
title Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
spellingShingle Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
Natali, A.
Insulin clearance
Insulin secretion
Insulin sensitivity
Nitric oxide
Internal Medicine
Endocrinology, Diabetes and Metabolism
SDG 3 - Good Health and Well-being
title_short Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
title_full Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
title_fullStr Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
title_full_unstemmed Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
title_sort Systemic inhibition of nitric oxide synthesis in non-diabetic individuals produces a significant deterioration in glucose tolerance by increasing insulin clearance and inhibiting insulin secretion
author Natali, A.
author_facet Natali, A.
Ribeiro, R.
Baldi, S.
Tulipani, A.
Rossi, M.
Venturi, E.
Mari, A.
Macedo, M. P.
Ferrannini, E.
author_role author
author2 Ribeiro, R.
Baldi, S.
Tulipani, A.
Rossi, M.
Venturi, E.
Mari, A.
Macedo, M. P.
Ferrannini, E.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Natali, A.
Ribeiro, R.
Baldi, S.
Tulipani, A.
Rossi, M.
Venturi, E.
Mari, A.
Macedo, M. P.
Ferrannini, E.
dc.subject.por.fl_str_mv Insulin clearance
Insulin secretion
Insulin sensitivity
Nitric oxide
Internal Medicine
Endocrinology, Diabetes and Metabolism
SDG 3 - Good Health and Well-being
topic Insulin clearance
Insulin secretion
Insulin sensitivity
Nitric oxide
Internal Medicine
Endocrinology, Diabetes and Metabolism
SDG 3 - Good Health and Well-being
description Funding Information: Source of funding The study received partial support from FTC (Fundação para a Ciência e a Tecnologia - Portuguese Foundation for Science and Technology) under the project PTDC/DTP-EPI/0207/2012. Other funds came from resources made available by other funded studies.
publishDate 2013
dc.date.none.fl_str_mv 2013-05
2013-05-01T00:00:00Z
2024-10-26T01:22:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/174097
url http://hdl.handle.net/10362/174097
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0012-186X
PURE: 101917900
https://doi.org/10.1007/s00125-013-2836-x
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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