Cholesterol reduction ameliorates glucose-induced calcium handling and insulin secretion in islets from low-density lipoprotein receptor, knockout mice

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dc.contributor.author Souza, J. C.
dc.contributor.author Vanzela, E. C.
dc.contributor.author Ribeiro, R. A.
dc.contributor.author Rezende, L. F.
dc.contributor.author Oliveira, C. A. de [UNIFESP]
dc.contributor.author Carneiro, E. M.
dc.contributor.author Oliveira, H. C. F.
dc.contributor.author Boschero, A. C.
dc.date.accessioned 2016-01-24T14:31:31Z
dc.date.available 2016-01-24T14:31:31Z
dc.date.issued 2013-04-01
dc.identifier http://dx.doi.org/10.1016/j.bbalip.2012.12.013
dc.identifier.citation Biochimica Et Biophysica Acta-molecular and Cell Biology of Lipids. Amsterdam: Elsevier B.V., v. 1831, n. 4, p. 769-775, 2013.
dc.identifier.issn 1388-1981
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36155
dc.description.abstract Aims/hypothesis: Changes in cellular cholesterol level may contribute to beta cell dysfunction. Islets from low density lipoprotein receptor knockout (LDLR-/-) mice have higher cholesterol content and secrete less insulin than wild-type (WT) mice. Here, we investigated the association between cholesterol content, insulin secretion and Ca2+ handling in these islets.Methods: Isolated islets from both LDLR-/- and WT mice were used for measurements of insulin secretion (radioimmunoassay), cholesterol content (fluorimetric assay), cytosolic Ca2+ level (fura-2AM) and SNARE protein expression (VAMP-2, SNAP-25 and syntaxin-1A). Cholesterol was depleted by incubating the islets with increasing concentrations (0-10 mmol/l) of methyl-beta-cyclodextrin (M beta CD).Results: the first and second phases of glucose-stimulated insulin secretion (GSIS) were lower in LDLR-/- than in WT islets, paralleled by an impairment of Ca2+ handling in the former. SNAP-25 and VAMP-2, but not syntaxin-1A, were reduced in LDLR-/- compared with WT islets. Removal of excess cholesterol from LDLR-/- islets normalized glucose- and tolbutamide-induced insulin release. Glucose-stimulated Ca2+ handling was also normalized in cholesterol-depleted LDLR-/- islets. Cholesterol removal from WT islets by 0.1 and 1.0 mmol/l M beta CD impaired both GSIS and Ca2+ handling. in addition, at 10 mmol/l M beta CD WT islet showed a loss of membrane integrity and higher DNA fragmentation.Conclusion: Abnormally high (LDLR-/- islets) or low cholesterol content (WT islets treated with M beta CD) alters both GSIS and Ca2+ handling. Normalization of cholesterol improves Ca2+ handling and insulin secretion in LDLR-/- islets. (C) 2013 Elsevier B.V. All rights reserved. en
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Instituto Nacional de Ciencia e Tecnologia de Obesidade e Diabetes
dc.format.extent 769-775
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Biochimica Et Biophysica Acta-molecular and Cell Biology of Lipids
dc.rights Acesso restrito
dc.subject Calcium handling en
dc.subject Cholesterol en
dc.subject Glucose en
dc.subject Insulin secretion en
dc.subject LDLR-/- mice en
dc.subject SNARE proteins en
dc.title Cholesterol reduction ameliorates glucose-induced calcium handling and insulin secretion in islets from low-density lipoprotein receptor, knockout mice en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Universidade Estadual de Campinas (UNICAMP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Struct & Funct Biol, BR-13083970 Campinas, SP, Brazil
dc.description.affiliation Fed Univ São Paulo Unifesp, Dept Biosci, Santos, SP, Brazil
dc.description.affiliationUnifesp Fed Univ São Paulo Unifesp, Dept Biosci, Santos, SP, Brazil
dc.identifier.doi 10.1016/j.bbalip.2012.12.013
dc.description.source Web of Science
dc.identifier.wos WOS:000316438200011



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