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A 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Model

2020-04-28Artigo científico Acesso aberto
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dc.contributor.authorSacramento, Joana F
dc.contributor.authorMartins, Fátima O
dc.contributor.authorRodrigues, Tiago
dc.contributor.authorMatafome, Paulo
dc.contributor.authorRibeiro, Maria J
dc.contributor.authorOlea, Elena
dc.contributor.authorConde, Silvia V
dc.contributor.authorV Conde, Silvia
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblFrontiers Media
dc.date.accessioned2020-05-18T22:32:59Z
dc.date.available2020-05-18T22:32:59Z
dc.date.issued2020-04-28
dc.descriptionThe present study was supported by the Portuguese Society of Diabetes. JS was supported by a PhD Grant from the Portuguese Foundation for Science and Technology, PD/BD/105890/2014.
dc.description.abstractEpidemiological 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1749685
dc.identifier.doi10.3389/fendo.2020.00262
dc.identifier.issn1664-2392
dc.identifier.otherPURE: 18212702
dc.identifier.otherPURE UUID: ceacde28-1872-4766-b837-7730c799f417
dc.identifier.otherPubMed: 32411098
dc.identifier.otherPubMedCentral: PMC7198774
dc.identifier.otherScopus: 85084475825
dc.identifier.otherWOS: 000533391800001
dc.identifier.otherORCID: /0000-0002-5920-5700/work/111135953
dc.identifier.urihttp://hdl.handle.net/10362/97935
dc.language.isoeng
dc.peerreviewedyes
dc.subjectSDG 3 - Good Health and Well-being
dc.titleA 2 Adenosine Receptors Mediate Whole-Body Insulin Sensitivity in a Prediabetes Animal Modelen
dc.title.subtitlePrimary Effects on Skeletal Muscleen
dc.typejournal article
degois.publication.titleFRONTIERS IN ENDOCRINOLOGY
degois.publication.volume11
dspace.entity.typePublication
person.familyNameVilares Conde
person.givenNameSilvia
person.identifier154176
person.identifier.ciencia-id561E-CF29-600A
person.identifier.orcid0000-0002-5920-5700
person.identifier.scopus-author-id7004283202
rcaap.rightsopenAccess
relation.isAuthorOfPublication898e99d8-61a5-44bc-878a-5e1ac44ca37c
relation.isAuthorOfPublication.latestForDiscovery898e99d8-61a5-44bc-878a-5e1ac44ca37c

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