Article

Download article 		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
Year: 2010
Is part of: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v. 1801, p. 183 - 190
DOI: https://doi.org/10.1016/j.bbalip.2009.10.012

Citation: 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; Primary hypercholesterolaemia impairs glucose homeostasis and insulin secretion in low-density lipoprotein receptor knockout mice independently of high-fat diet and obesity. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, v.1801, p. 183-190, 2010

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 glucos-estimulated 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. (C) 2009 Elsevier B.V. All rights reserved.

Keywords: Cholesterol; glucose homeostasis; hypercholesterolemia; insulin secretion; LDL receptor; pancreatic islet;
Subjects: CIENCIAS_BIOLOGICAS; Fisiologia Geral; Metabolismo de Lípides e Lipoproteínas; CIENCIAS_BIOLOGICAS; Bioquímica; Metabolismo e Bioenergética; CIENCIAS_BIOLOGICAS; Bioquímica; Metabolismo e Bioenergética; Metabolismo de carboidratos;

Funding: This study is part of the PhD Thesis of ML Bonfleur and was supported by grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico (CNPq/INCT National Institute for Diabetes and Obesity) and Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES). We are grateful to Ricardo Beltrame de Oliveira for helping in the morphometric analyses, to Lescio D. Teixeira for animal care and Nicola Conran for editing the English. 		Financed by: