Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits

Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits

Author Helfenstein, Tatiana Autor UNIFESP Google Scholar
Fonseca, Francisco A. Autor UNIFESP Google Scholar
Ihara, Silvia S. Autor UNIFESP Google Scholar
Bottos, Juliana M. Autor UNIFESP Google Scholar
Moreira, Flavio T. Autor UNIFESP Google Scholar
Pott, Henrique Google Scholar
Farah, Michel E. Autor UNIFESP Google Scholar
Martins, Maria C. Autor UNIFESP Google Scholar
Izar, Maria C. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade Estadual de Campinas (UNICAMP)
Abstract P>With the increasing prevalence of diabetes mellitus and metabolic syndrome worldwide, experimental models are required to better understand the pathophysiology and therapeutic approaches to preserve pancreatic beta cells, attenuate atherosclerosis and protect target organs. the aims of this study were to develop an experimental model of impaired glucose tolerance combined with hypercholesterolaemia induced by diet and assess metabolic alterations and target organ lesions. New Zealand male rabbits were fed high-fat/high-sucrose (10/40%) and cholesterol-enriched diet for 24 weeks, when they were sacrificed. Biochemistry, fundus photographs with fluorescein angiography and pathological analyses were performed. Cholesterol-fed and normal animals of same age were compared. Results: the animals with diet-induced impaired glucose tolerance combined with hypercholesterolaemia gained weight, increased blood glucose, total cholesterol, LDL-C and triglycerides and decreased HDL-C (P < 0.05 vs. baseline). Fructosamine levels and the homeostasis model assessment of insulin resistance (HOMA-IR) index were increased, while there was a reduction in the HOMA-beta (P < 0.05 for all vs. baseline). Histomorphologic findings of this model were aortic atherosclerosis, hepatic steatofibrosis and glomerular macrophage infiltration. Early clinical features of diabetic retinopathy with hyperfluorescent dots consistent with presence of retina microaneurysms were seen since week 12, progressing up to the end of the experiment (P < 0.0005 vs. baseline and 12 weeks). Our model reproduced several metabolic characteristics of human diabetes mellitus and promoted early signs of retinopathy. This non-expensive model is suitable for studying mechanistic pathways and allowing novel strategic approaches.
Keywords animal models
diet
impaired glucose tolerance
insulin resistance
retinopathy
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Date 2011-02-01
Published in International Journal of Experimental Pathology. Malden: Wiley-Blackwell Publishing, Inc, v. 92, n. 1, p. 40-49, 2011.
ISSN 0959-9673 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 40-49
Origin http://dx.doi.org/10.1111/j.1365-2613.2010.00753.x
Access rights Closed access
Type Article
Web of Science ID WOS:000286671200005
URI http://repositorio.unifesp.br/handle/11600/33438

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