Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice

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dc.contributor.authorCarvalho, Carolina Prado de França [UNIFESP]
dc.contributor.authorOliveira, R. B.
dc.contributor.authorBritan, A.
dc.contributor.authorSantos-Silva, J. C.
dc.contributor.authorBoschero, A. C.
dc.contributor.authorMeda, P.
dc.contributor.authorCollares-Buzato, C. B.
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniv Geneva
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:27:23Z
dc.date.available2016-01-24T14:27:23Z
dc.date.issued2012-07-01
dc.description.abstractCarvalho CP, Oliveira RB, Britan A, Santos-Silva JC, Boschero AC, Meda P, Collares-Buzato CB. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. Am J Physiol Endocrinol Metab 303: E144-E151, 2012. First published May 8, 2012; doi: 10.1152/ajpendo.00489.2011.-Gap junctional intercellular communication between beta-cells is crucial for proper insulin biosynthesis and secretion. the aim of this work was to investigate the expression of connexin (Cx) 36 at the protein level as well as the function and structure of gap junctions (GJ) made by this protein in the endocrine pancreas of prediabetic mice. C57BL/6 mice were fed a high-fat (HF) or regular chow diet for 60 days. HF-fed mice became obese and prediabetic, as shown by peripheral insulin resistance, moderate hyperglycemia, hyperinsulinemia, and compensatory increase in endocrine pancreas mass. Compared with control mice, prediabetic animals showed a significant decrease in insulin-secretory response to glucose and displayed a significant reduction in islet Cx36 protein. Ultrastructural analysis further showed that prediabetic mice had GJ plaques about one-half the size of those of the control group. Microinjection of isolated pancreatic islets with ethidium bromide revealed that prediabetic mice featured a beta-cell-beta-cell coupling 30% lower than that of control animals. We conclude that beta-cell-beta-cell coupling mediated by Cx36 made-channels is impaired in prediabetic mice, suggesting a role of Cx36-dependent cell-to-cell communication in the pathogenesis of the early beta-cell dysfunctions that lead to type 2-diabetes.en
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Histol & Embryol, UNICAMP, BR-13083970 Campinas, SP, Brazil
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Physiol & Biophys, BR-1303970 Campinas, SP, Brazil
dc.description.affiliationUniv Geneva, Sch Med, Dept Cell Physiol & Metab, CH-1211 Geneva, Switzerland
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biosci, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biosci, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipSwiss National Science Foundation
dc.description.sponsorshipJuvenile Diabetes Research Foundation
dc.description.sponsorshipEuropean Union
dc.description.sponsorshipIDFAPESP: 2006/50758-3
dc.description.sponsorshipIDFAPESP: 2009/52824-1
dc.description.sponsorshipIDFAPESP: 2010/50789-1
dc.description.sponsorshipIDCNPq: 201862/207-7
dc.description.sponsorshipIDSwiss National Science Foundation: 310030_141162
dc.description.sponsorshipIDSwiss National Science Foundation: CR32I3_129987
dc.description.sponsorshipIDJuvenile Diabetes Research Foundation: 40-2011-11
dc.description.sponsorshipIDEuropean Union: BETAIMAGE 222980
dc.description.sponsorshipIDEuropean Union: IMI, IMIDIA, C2008-T7
dc.format.extentE144-E151
dc.identifierhttps://dx.doi.org/10.1152/ajpendo.00489.2011
dc.identifier.citationAmerican Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 303, n. 1, p. E144-E151, 2012.
dc.identifier.doi10.1152/ajpendo.00489.2011
dc.identifier.issn0193-1849
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35022
dc.identifier.wosWOS:000306412000013
dc.language.isoeng
dc.publisherAmer Physiological Soc
dc.relation.ispartofAmerican Journal of Physiology-endocrinology and Metabolism
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectHigh-fat-fed miceen
dc.subjectType 2 diabetes mellitusen
dc.subjectConnexin 36en
dc.subjectConnexinsen
dc.subjectCell-cell communicationen
dc.subjectInsulin secretionen
dc.subjectInsulin resistanceen
dc.subjectBeta-cell dysfunctionen
dc.titleImpaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic miceen
dc.typeinfo:eu-repo/semantics/article
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