Acute glucagon induces postprandial peripheral insulin resistance
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/21488 |
Resumo: | This study was supported by Fundacao para a Ciencia e Tecnologia (FCT) grant PIC/IC/82956/2007, PTDC/BIM-MET/0486/2012, PTDC/DTP-EPI/0207/2012 and by the Portuguese Diabetes Society (SPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
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7160 |
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Acute glucagon induces postprandial peripheral insulin resistanceRAT-LIVERSENSITIVITYNITRIC-OXIDEPHOSPHODIESTERASESSECRETIONHEPATIC GLUTATHIONEHYPERGLYCEMIAPULSATILE INSULINBETA-CELLGLUCOSE CLEARANCESDG 3 - Good Health and Well-beingThis study was supported by Fundacao para a Ciencia e Tecnologia (FCT) grant PIC/IC/82956/2007, PTDC/BIM-MET/0486/2012, PTDC/DTP-EPI/0207/2012 and by the Portuguese Diabetes Society (SPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Glucagon levels are often moderately elevated in diabetes. It is known that glucagon leads to a decrease in hepatic glutathione (GSH) synthesis that in turn is associated with decreased postprandial insulin sensitivity. Given that cAMP pathway controls GSH levels we tested whether insulin sensitivity decreases after intraportal (ipv) administration of a cAMP analog (DBcAMP), and investigated whether glucagon promotes insulin resistance through decreasing hepatic GSH levels. Insulin sensitivity was determined in fed male SpragueDawley rats using a modified euglycemic hyperinsulinemic clamp in the postprandial state upon ipv administration of DBcAMP as well as glucagon infusion. Glucagon effects on insulin sensitivity was assessed in the presence or absence of postprandial insulin sensitivity inhibition by administration of L-NMMA. Hepatic GSH and NO content and plasma levels of NO were measured after acute ipv glucagon infusion. Insulin sensitivity was assessed in the fed state and after ipv glucagon infusion in the presence of GSH-E. We founf that DBcAMP and glucagon produce a decrease of insulin sensitivity, in a dose-dependent manner. Glucagon-induced decrease of postprandial insulin sensitivity correlated with decreased hepatic GSH content and was restored by administration of GSH-E. Furthermore, inhibition of postprandial decrease of insulin sensitivity L-NMMA was not overcome by glucagon, but glucagon did not affect hepatic and plasma levels of NO. These results show that glucagon decreases postprandial insulin sensitivity through reducing hepatic GSH levels, an effect that is mimicked by increasing cAMP hepatic levels and requires physiological NO levels. These observations support the hypothesis that glucagon acts via adenylate cyclase to decrease hepatic GSH levels and induce insulin resistance. We suggest that the glucagon-cAMP-GSH axis is a potential therapeutic target to address insulin resistance in pathological conditions.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNPatarrão, Rita S.Macedo, M. Paula2017-06-08T22:01:04Z2015-01-012015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/21488eng1932-6203PURE: 482128https://doi.org/10.1371/journal.pone.0127221info: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:RCAAP2024-03-11T04:08:13Zoai:run.unl.pt:10362/21488Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:26:49.167994Repositório 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 |
Acute glucagon induces postprandial peripheral insulin resistance |
title |
Acute glucagon induces postprandial peripheral insulin resistance |
spellingShingle |
Acute glucagon induces postprandial peripheral insulin resistance Patarrão, Rita S. RAT-LIVER SENSITIVITY NITRIC-OXIDE PHOSPHODIESTERASES SECRETION HEPATIC GLUTATHIONE HYPERGLYCEMIA PULSATILE INSULIN BETA-CELL GLUCOSE CLEARANCE SDG 3 - Good Health and Well-being |
title_short |
Acute glucagon induces postprandial peripheral insulin resistance |
title_full |
Acute glucagon induces postprandial peripheral insulin resistance |
title_fullStr |
Acute glucagon induces postprandial peripheral insulin resistance |
title_full_unstemmed |
Acute glucagon induces postprandial peripheral insulin resistance |
title_sort |
Acute glucagon induces postprandial peripheral insulin resistance |
author |
Patarrão, Rita S. |
author_facet |
Patarrão, Rita S. Macedo, M. Paula |
author_role |
author |
author2 |
Macedo, M. Paula |
author2_role |
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 |
Patarrão, Rita S. Macedo, M. Paula |
dc.subject.por.fl_str_mv |
RAT-LIVER SENSITIVITY NITRIC-OXIDE PHOSPHODIESTERASES SECRETION HEPATIC GLUTATHIONE HYPERGLYCEMIA PULSATILE INSULIN BETA-CELL GLUCOSE CLEARANCE SDG 3 - Good Health and Well-being |
topic |
RAT-LIVER SENSITIVITY NITRIC-OXIDE PHOSPHODIESTERASES SECRETION HEPATIC GLUTATHIONE HYPERGLYCEMIA PULSATILE INSULIN BETA-CELL GLUCOSE CLEARANCE SDG 3 - Good Health and Well-being |
description |
This study was supported by Fundacao para a Ciencia e Tecnologia (FCT) grant PIC/IC/82956/2007, PTDC/BIM-MET/0486/2012, PTDC/DTP-EPI/0207/2012 and by the Portuguese Diabetes Society (SPD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-01-01 2015-01-01T00:00:00Z 2017-06-08T22:01:04Z |
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/10362/21488 |
url |
http://hdl.handle.net/10362/21488 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1932-6203 PURE: 482128 https://doi.org/10.1371/journal.pone.0127221 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
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 |
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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 |
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1799137897581903872 |