A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle

Detalhes bibliográficos
Autor(a) principal: Sacramento, Joana F.
Data de Publicação: 2020
Outros Autores: Martins, Fátima O., Rodrigues, Tiago, Matafome, Paulo N., Ribeiro, Maria J., Olea, Elena, Conde, Sílvia 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/10316/106106
https://doi.org/10.3389/fendo.2020.00262
Resumo: Epidemiological studies showed that chronic caffeine intake decreased the risk of type 2 diabetes. Previously, we described that chronic caffeine intake prevents and reverses insulin resistance induced by hypercaloric diets and aging, in rats. Caffeine has several cellular mechanisms of action, being the antagonism of adenosine receptors the only attained with human coffee consumption. Here, we investigated the subtypes of adenosine receptors involved on the effects of chronic caffeine intake on insulin sensitivity and the mechanisms and sex differences behind this effect. Experiments were performed in male and female Wistar rats fed either a chow or high-sucrose (HSu) diet (35% of sucrose in drinking water) during 28 days, to induce insulin resistance. In the last 15 days of diet the animals were submitted to DPCPX (A1 antagonist, 0.4 mg/kg), SCH58261 (A2A antagonist, 0.5 mg/kg), or MRS1754 (A2B antagonist, 9.5 μg/kg) administration. Insulin sensitivity, fasting glycaemia, blood pressure, catecholamines, and fat depots were assessed. Expression of A1, A2A, A2B adenosine receptors and protein involved in insulin signaling pathways were evaluated in the liver, skeletal muscle, and visceral adipose tissue. UCP1 expression was measured in adipose tissue. Paradoxically, SCH58261 and MRS1754 decreased insulin sensitivity in control animals, whereas they both improved insulin response in HSu diet animals. DPCPX did not alter significantly insulin sensitivity in control or HSu animals, but reversed the increase in total and visceral fat induced by the HSu diet. In skeletal muscle, A1, A2A, and A2B adenosine receptor expression were increased in HSu group, an effect that was restored by SCH58261 and MRS1754. In the liver, A1, A2A expression was increased in HSu group, while A2B expression was decreased, being this last effect reversed by administration of MRS1754. In adipose tissue, A1 and A2A block upregulated the expression of these receptors. A2 adenosine antagonists restored impaired insulin signaling in the skeletal muscle of HSu rats, but did not affect liver or adipose insulin signaling. Our results show that adenosine receptors exert opposite effects on insulin sensitivity, in control and insulin resistant states and strongly suggest that A2 adenosine receptors in the skeletal muscle are the majors responsible for whole-body insulin sensitivity.
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spelling A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscleadenosineadenosine receptorsinsulin resistanceinsulin signalingadipose tissueskeletal musclegender differencesEpidemiological studies showed that chronic caffeine intake decreased the risk of type 2 diabetes. Previously, we described that chronic caffeine intake prevents and reverses insulin resistance induced by hypercaloric diets and aging, in rats. Caffeine has several cellular mechanisms of action, being the antagonism of adenosine receptors the only attained with human coffee consumption. Here, we investigated the subtypes of adenosine receptors involved on the effects of chronic caffeine intake on insulin sensitivity and the mechanisms and sex differences behind this effect. Experiments were performed in male and female Wistar rats fed either a chow or high-sucrose (HSu) diet (35% of sucrose in drinking water) during 28 days, to induce insulin resistance. In the last 15 days of diet the animals were submitted to DPCPX (A1 antagonist, 0.4 mg/kg), SCH58261 (A2A antagonist, 0.5 mg/kg), or MRS1754 (A2B antagonist, 9.5 μg/kg) administration. Insulin sensitivity, fasting glycaemia, blood pressure, catecholamines, and fat depots were assessed. Expression of A1, A2A, A2B adenosine receptors and protein involved in insulin signaling pathways were evaluated in the liver, skeletal muscle, and visceral adipose tissue. UCP1 expression was measured in adipose tissue. Paradoxically, SCH58261 and MRS1754 decreased insulin sensitivity in control animals, whereas they both improved insulin response in HSu diet animals. DPCPX did not alter significantly insulin sensitivity in control or HSu animals, but reversed the increase in total and visceral fat induced by the HSu diet. In skeletal muscle, A1, A2A, and A2B adenosine receptor expression were increased in HSu group, an effect that was restored by SCH58261 and MRS1754. In the liver, A1, A2A expression was increased in HSu group, while A2B expression was decreased, being this last effect reversed by administration of MRS1754. In adipose tissue, A1 and A2A block upregulated the expression of these receptors. A2 adenosine antagonists restored impaired insulin signaling in the skeletal muscle of HSu rats, but did not affect liver or adipose insulin signaling. Our results show that adenosine receptors exert opposite effects on insulin sensitivity, in control and insulin resistant states and strongly suggest that A2 adenosine receptors in the skeletal muscle are the majors responsible for whole-body insulin sensitivity.Frontiers Media S.A.2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106106http://hdl.handle.net/10316/106106https://doi.org/10.3389/fendo.2020.00262eng1664-239232411098Sacramento, Joana F.Martins, Fátima O.Rodrigues, TiagoMatafome, Paulo N.Ribeiro, Maria J.Olea, ElenaConde, Sílvia V.info: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:RCAAP2023-03-21T21:34:39Zoai:estudogeral.uc.pt:10316/106106Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:34.334972Repositório 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 A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
title A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
spellingShingle A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
Sacramento, Joana F.
adenosine
adenosine receptors
insulin resistance
insulin signaling
adipose tissue
skeletal muscle
gender differences
title_short A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
title_full A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
title_fullStr A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
title_full_unstemmed A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
title_sort A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model: Primary Effects on Skeletal Muscle
author Sacramento, Joana F.
author_facet Sacramento, Joana F.
Martins, Fátima O.
Rodrigues, Tiago
Matafome, Paulo N.
Ribeiro, Maria J.
Olea, Elena
Conde, Sílvia V.
author_role author
author2 Martins, Fátima O.
Rodrigues, Tiago
Matafome, Paulo N.
Ribeiro, Maria J.
Olea, Elena
Conde, Sílvia V.
author2_role author
author
author
author
author
author
dc.contributor.author.fl_str_mv Sacramento, Joana F.
Martins, Fátima O.
Rodrigues, Tiago
Matafome, Paulo N.
Ribeiro, Maria J.
Olea, Elena
Conde, Sílvia V.
dc.subject.por.fl_str_mv adenosine
adenosine receptors
insulin resistance
insulin signaling
adipose tissue
skeletal muscle
gender differences
topic adenosine
adenosine receptors
insulin resistance
insulin signaling
adipose tissue
skeletal muscle
gender differences
description Epidemiological studies showed that chronic caffeine intake decreased the risk of type 2 diabetes. Previously, we described that chronic caffeine intake prevents and reverses insulin resistance induced by hypercaloric diets and aging, in rats. Caffeine has several cellular mechanisms of action, being the antagonism of adenosine receptors the only attained with human coffee consumption. Here, we investigated the subtypes of adenosine receptors involved on the effects of chronic caffeine intake on insulin sensitivity and the mechanisms and sex differences behind this effect. Experiments were performed in male and female Wistar rats fed either a chow or high-sucrose (HSu) diet (35% of sucrose in drinking water) during 28 days, to induce insulin resistance. In the last 15 days of diet the animals were submitted to DPCPX (A1 antagonist, 0.4 mg/kg), SCH58261 (A2A antagonist, 0.5 mg/kg), or MRS1754 (A2B antagonist, 9.5 μg/kg) administration. Insulin sensitivity, fasting glycaemia, blood pressure, catecholamines, and fat depots were assessed. Expression of A1, A2A, A2B adenosine receptors and protein involved in insulin signaling pathways were evaluated in the liver, skeletal muscle, and visceral adipose tissue. UCP1 expression was measured in adipose tissue. Paradoxically, SCH58261 and MRS1754 decreased insulin sensitivity in control animals, whereas they both improved insulin response in HSu diet animals. DPCPX did not alter significantly insulin sensitivity in control or HSu animals, but reversed the increase in total and visceral fat induced by the HSu diet. In skeletal muscle, A1, A2A, and A2B adenosine receptor expression were increased in HSu group, an effect that was restored by SCH58261 and MRS1754. In the liver, A1, A2A expression was increased in HSu group, while A2B expression was decreased, being this last effect reversed by administration of MRS1754. In adipose tissue, A1 and A2A block upregulated the expression of these receptors. A2 adenosine antagonists restored impaired insulin signaling in the skeletal muscle of HSu rats, but did not affect liver or adipose insulin signaling. Our results show that adenosine receptors exert opposite effects on insulin sensitivity, in control and insulin resistant states and strongly suggest that A2 adenosine receptors in the skeletal muscle are the majors responsible for whole-body insulin sensitivity.
publishDate 2020
dc.date.none.fl_str_mv 2020
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/10316/106106
http://hdl.handle.net/10316/106106
https://doi.org/10.3389/fendo.2020.00262
url http://hdl.handle.net/10316/106106
https://doi.org/10.3389/fendo.2020.00262
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1664-2392
32411098
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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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
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