Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function

Detalhes bibliográficos
Autor(a) principal: Tavares, Gabriela
Data de Publicação: 2021
Outros Autores: Martins, Fatima O., Melo, Bernardete F., Matafome, Paulo, Conde, Silvia V.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/127176
Resumo: Funding: This work was supported by a grant from GIFT (Grupo de Investigacao Fundamental e Translacional) from the Portuguese Society of Diabetes. G.T and B.F.M. were supported by PhD Grants from the Portuguese Foundation for Science and Technology, Reference PD/BD/127822/2016 and PD/BD/128336/2017, respectively. FOM is supported by the Portuguese Foundation for Science and Technology, contract CEECIND/04266/2017.
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spelling Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic FunctionD1 dopamine receptorD2 dopamine receptordopamineglucose metabolisminsulin signalinglipid metabolismPharmacologyPharmacology (medical)SDG 3 - Good Health and Well-beingFunding: This work was supported by a grant from GIFT (Grupo de Investigacao Fundamental e Translacional) from the Portuguese Society of Diabetes. G.T and B.F.M. were supported by PhD Grants from the Portuguese Foundation for Science and Technology, Reference PD/BD/127822/2016 and PD/BD/128336/2017, respectively. FOM is supported by the Portuguese Foundation for Science and Technology, contract CEECIND/04266/2017.Dopamine is a key regulator of glucose metabolism in the central nervous system. However, dopamine is also present in the periphery and may have direct effects on insulin-sensitive tissues. Dopamine receptor 2 (D2R) agonist bromocriptine is a FDA-approved drug for type 2 diabetes. Herein, we explored the role of peripheral dopamine and its receptors in regulating glucose uptake and metabolism on insulin-sensitive tissues. Peripheral dopamine effect in [3H]2-deoxyglucose uptake in insulin-sensitive tissues was tested in vivo in rats. Direct effects on [3H]2-deoxyglucose uptake, insulin receptor phosphorylation, and regulation of metabolic function were tested ex vivo in the liver, soleus muscle, and white and brown adipose tissues. Bromocriptine and the antagonists domperidone, D2R antagonist, and haloperidol, antagonist of both dopamine receptor 1 (D1R) and D2R, were used to disclose dopamine receptors’ involvement. Peripheral dopamine increases glucose uptake in vivo. Ex vivo, only dopamine increased glucose uptake in the soleus, while bromocriptine increased it in the liver; the effects were reverted by haloperidol and domperidone, respectively. In adipose tissue, domperidone reverted dopamine- and bromocriptine-mediated potentiation of insulin-induced glucose uptake, but in turn increased the insulin receptor, Akt, AMPK, HSL, ACC, and ACL, phosphorylation. In the soleus muscle, AMPK-phosphorylation increased with bromocriptine and dopamine whose effects were suppressed by domperidone and haloperidol. In conclusion, peripheral dopamine stimulates glucose uptake with its receptors being differentially involved in glucose uptake in insulin-sensitive tissues. Dopamine also has a role in lipid metabolism in white adipose tissue. Altogether, these results suggest that peripheral modulation of the dopaminergic system should be further evaluated as a putative therapeutic approach for metabolic disorders.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNTavares, GabrielaMartins, Fatima O.Melo, Bernardete F.Matafome, PauloConde, Silvia V.2021-11-04T23:38:17Z2021-09-092021-09-09T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/127176eng1663-9812PURE: 34203821https://doi.org/10.3389/fphar.2021.713418info: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:RCAAP2024-05-22T17:56:59Zoai:run.unl.pt:10362/127176Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T17:56:59Repositório 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 Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
title Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
spellingShingle Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
Tavares, Gabriela
D1 dopamine receptor
D2 dopamine receptor
dopamine
glucose metabolism
insulin signaling
lipid metabolism
Pharmacology
Pharmacology (medical)
SDG 3 - Good Health and Well-being
title_short Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
title_full Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
title_fullStr Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
title_full_unstemmed Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
title_sort Peripheral Dopamine Directly Acts on Insulin-Sensitive Tissues to Regulate Insulin Signaling and Metabolic Function
author Tavares, Gabriela
author_facet Tavares, Gabriela
Martins, Fatima O.
Melo, Bernardete F.
Matafome, Paulo
Conde, Silvia V.
author_role author
author2 Martins, Fatima O.
Melo, Bernardete F.
Matafome, Paulo
Conde, Silvia V.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Tavares, Gabriela
Martins, Fatima O.
Melo, Bernardete F.
Matafome, Paulo
Conde, Silvia V.
dc.subject.por.fl_str_mv D1 dopamine receptor
D2 dopamine receptor
dopamine
glucose metabolism
insulin signaling
lipid metabolism
Pharmacology
Pharmacology (medical)
SDG 3 - Good Health and Well-being
topic D1 dopamine receptor
D2 dopamine receptor
dopamine
glucose metabolism
insulin signaling
lipid metabolism
Pharmacology
Pharmacology (medical)
SDG 3 - Good Health and Well-being
description Funding: This work was supported by a grant from GIFT (Grupo de Investigacao Fundamental e Translacional) from the Portuguese Society of Diabetes. G.T and B.F.M. were supported by PhD Grants from the Portuguese Foundation for Science and Technology, Reference PD/BD/127822/2016 and PD/BD/128336/2017, respectively. FOM is supported by the Portuguese Foundation for Science and Technology, contract CEECIND/04266/2017.
publishDate 2021
dc.date.none.fl_str_mv 2021-11-04T23:38:17Z
2021-09-09
2021-09-09T00:00:00Z
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/10362/127176
url http://hdl.handle.net/10362/127176
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1663-9812
PURE: 34203821
https://doi.org/10.3389/fphar.2021.713418
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 mluisa.alvim@gmail.com
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