Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/89779
Type: Artigo de periódico
Title: Cholesterol Reduction Ameliorates Glucose-induced Calcium Handling And Insulin Secretion In Islets From Low-density Lipoprotein Receptor Knockout Mice
Author: Souza J.C.
Vanzela E.C.
Ribeiro R.A.
Rezende L.F.
De Oliveira C.A.
Carneiro E.M.
Oliveira H.C.F.
Boschero A.C.
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 (MβCD). 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 MβCD impaired both GSIS and Ca2 + handling. In addition, at 10 mmol/l MβCD 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 MβCD) alters both GSIS and Ca2 + handling. Normalization of cholesterol improves Ca2 + handling and insulin secretion in LDLR-/- islets. © 2013 Elsevier B.V.
Editor: 
Rights: fechado
Identifier DOI: 10.1016/j.bbalip.2012.12.013
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-84873440296&partnerID=40&md5=7d25ba9227328f7e09e391a567ef2e7f
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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