High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets

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dc.contributor.authorRafacho, Alex
dc.contributor.authorCestari, Tania M.
dc.contributor.authorTaboga, Sebastiao R. [UNESP]
dc.contributor.authorBoschero, Antonio C.
dc.contributor.authorBosqueiro, Jose R. [UNESP]
dc.contributor.institutionUniversidade Estadual de Campinas (UNICAMP)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T15:32:42Z
dc.date.available2014-05-20T15:32:42Z
dc.date.issued2009-04-01
dc.description.abstractRafacho A, Cestari TM, Taboga SR, Boschero AC, Bosqueiro JR. High doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat islets. Am J Physiol Endocrinol Metab 296: E681-E689, 2009. First published January 21, 2009; doi:10.1152/ajpendo.90931.2008.-Activation of insulin signaling and cell cycle intermediates is required for adult beta-cell proliferation. Here, we report a model to study beta-cell proliferation in living rats by administering three different doses of dexamethasone (0.1, 0.5, and 1.0 mg/kg ip, DEX 0.1, DEX 0.5, and DEX 1.0, respectively) for 5 days. Insulin sensitivity, insulin secretion, and histomorphometric data were investigated. Western blotting was used to analyze the levels of proteins related to the control of beta-cell growth. DEX 1.0 rats, which present moderate hyperglycemia and marked hyperinsulinemia, exhibited a 5.1-fold increase in beta-cell proliferation and an increase (17%) in beta-cell size, with significant increase in beta-cell mass, compared with control rats. The hyperinsulinemic but euglycemic DEX 0.5 rats also showed a significant 3.6-fold increase in beta-cell proliferation. However, DEX 0.1 rats, which exhibited the lowest degree of insulin resistance, compensate for insulin demand by improving only islet function. Activation of the insulin receptor substrate 2/phosphatidylinositol 3-kinase/serine-threoninekinase/ribosomalprotein S6 kinase pathway, as well as protein retinoblastoma in islets from DEX 1.0 and DEX 0.5, but not in DEX 0.1, rats was also observed. Therefore, increasing doses of dexamethasone induce three different degrees of insulin requirement in living rats, serving as a model to investigate compensatory beta-cell alterations. Augmented beta-cell mass involves beta-cell hyperplasia and, to a lower extent, beta-cell hypertrophy. We suggest that alterations in circulating insulin and, to a lesser extent, glucose levels could be the major stimuli for beta-cell proliferation in the dexamethasone-induced insulin resistance.en
dc.description.affiliationUniv Estadual Campinas, Inst Biol, Dept Physiol & Biophys, São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Sch Dent Bauru, Dept Biol Sci, São Paulo, Brazil
dc.description.affiliationSão Paulo State Univ, Dept Phys Educ, Sch Sci, São Paulo, Brazil
dc.description.affiliationSão Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ, Dept Phys Educ, Sch Sci, São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Biol, São Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extentE681-E689
dc.identifierhttp://dx.doi.org/10.1152/ajpendo.90931.2008
dc.identifier.citationAmerican Journal of Physiology-endocrinology and Metabolism. Bethesda: Amer Physiological Soc, v. 296, n. 4, p. E681-E689, 2009.
dc.identifier.doi10.1152/ajpendo.90931.2008
dc.identifier.issn0193-1849
dc.identifier.orcid0000-0002-0970-4288
dc.identifier.urihttp://hdl.handle.net/11449/41546
dc.identifier.wosWOS:000264514900014
dc.language.isoeng
dc.publisherAmer Physiological Soc
dc.relation.ispartofAmerican Journal of Physiology: Endocrinology and Metabolism
dc.relation.ispartofjcr4.018
dc.relation.ispartofsjr2,140
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectbeta-cell growthen
dc.subjectglucocorticoiden
dc.subjecthyperglycemiaen
dc.subjecthyperinsulinemiaen
dc.subjectinsulin resistanceen
dc.titleHigh doses of dexamethasone induce increased beta-cell proliferation in pancreatic rat isletsen
dc.typeArtigo
dcterms.licensehttp://www.the-aps.org/mm/Publications/Info-For-Authors/Permissions
dcterms.rightsHolderAmer Physiological Soc
unesp.author.orcid0000-0003-3829-8570[4]
unesp.author.orcid0000-0002-8637-6097[1]
unesp.author.orcid0000-0002-0970-4288[3]
unesp.author.orcid0000-0001-5367-7427[5]

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