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Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits
Author(s) -
Helfenstein Tatiana,
Fonseca Francisco A.,
Ihara Sílvia S.,
Bottós Juliana M.,
Moreira Flávio T.,
Pott Jr Henrique,
Farah Michel E.,
Martins Maria C.,
Izar Maria C.
Publication year - 2011
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/j.1365-2613.2010.00753.x
Subject(s) - retina , impaired glucose tolerance , medicine , diabetes mellitus , endocrinology , biology , type 2 diabetes , neuroscience
Summary 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‐β ( 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.