Acute glucagon induces postprandial peripheral insulin resistance

Detalhes bibliográficos
Autor(a) principal: Patarrão, Rita S.
Data de Publicação: 2015
Outros Autores: Macedo, M. Paula
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.
id RCAP_6ac3b458794f370323237967c6e6a163
oai_identifier_str oai:run.unl.pt:10362/21488
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling 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
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
_version_ 1799137897581903872

Registros relacionados