Artículos de revistas
Primary Hypercholesterolaemia Impairs Glucose Homeostasis And Insulin Secretion In Low-density Lipoprotein Receptor Knockout Mice Independently Of High-fat Diet And Obesity.
Registro en:
Biochimica Et Biophysica Acta. v. 1801, n. 2, p. 183-90, 2010-Feb.
0006-3002
10.1016/j.bbalip.2009.10.012
19913637
Autor
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
Institución
Resumen
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. 1801 183-90