Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/199188
Type: Artigo de periódico
Title: Primary Hypercholesterolaemia Impairs Glucose Homeostasis And Insulin Secretion In Low-density Lipoprotein Receptor Knockout Mice Independently Of High-fat Diet And Obesity.
Author: Bonfleur, Maria Lúcia
Vanzela, Emerielle Cristine
Ribeiro, Rosane Aparecida
de Gabriel Dorighello, Gabriel
de França Carvalho, Carolina Prado
Collares-Buzato, Carla Beatriz
Carneiro, Everardo Magalhães
Boschero, Antonio Carlos
de Oliveira, Helena Coutinho Franco
Abstract: We investigated whether primary hypercholesterolaemia per se affects glucose homeostasis and insulin secretion in low-density lipoprotein receptor knockout mice (LDLR(-/-)). Glucose plasma levels were increased and insulin decreased in LDLR(-/-) compared to the wild-type mice. LDLR(-/-) mice presented impaired glucose tolerance, but normal whole body insulin sensitivity. The dose-response curve of glucose-stimulated insulin secretion was shifted to the right in LDLR(-/-) islets. Significant reductions in insulin secretion in response to l-leucine or 2-ketoisocaproic acid were also observed in LDLR(-/-). Islet morphometric parameters, total insulin and DNA content were similar in both groups. Glucose uptake and oxidation were reduced in LDLR(-/-) islets. Removal of cholesterol from LDLR(-/-) islets corrected glucose-stimulated insulin secretion. These results indicate that enhanced membrane cholesterol content due to hypercholesterolaemia leads to a lower insulin secretion and glucose intolerance without affecting body insulin sensitivity. This represents an additional risk factor for diabetes and atherosclerosis in primary hypercholesterolaemia.
Subject: Animals
Cholesterol
Dietary Fats
Female
Glucose
Glucose Tolerance Test
Homeostasis
Hypercholesterolemia
Insulin
Islets Of Langerhans
Leucine
Lipids
Male
Mice
Mice, Knockout
Obesity
Oxidation-reduction
Receptors, Ldl
Beta-cyclodextrins
Rights: fechado
Identifier DOI: 10.1016/j.bbalip.2009.10.012
Address: http://www.ncbi.nlm.nih.gov/pubmed/19913637
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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