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Rosiglitazone (PPARγ‐agonist) attenuates atherogenesis with no effect on hyperglycaemia in a combined diabetes–atherosclerosis mouse model
Author(s) -
Levi Z.,
Shaish A.,
Yacov N.,
Levkovitz H.,
Trestman S.,
Gerber Y.,
Cohen H.,
Dvir A.,
Rhachmani R.,
Ravid M.,
Harats D.
Publication year - 2003
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1046/j.1463-1326.2003.00240.x
Subject(s) - rosiglitazone , medicine , endocrinology , insulin resistance , streptozotocin , diabetes mellitus , agonist , apolipoprotein e , insulin , receptor , disease
Background: The administration of peroxisome proliferator‐activated receptor γ (PPARγ) agonists to low‐density lipoprotein (LDL)‐receptor‐deficient mice resulted in a reduction in the atherosclerotic lesion area in male mice, but not in female mice. The male mice also exhibited reduction in insulin resistance while the female mice did not. To further examine the relationship between PPARγ agonists, insulin resistance and atherosclerosis, we used the model of accelerated atherosclerosis in male apolipoprotein E (apoE)‐deficient mice rendered diabetic by low‐dose streptozotocin (STZ). Methods: Male, apoE‐deficient mice ( n = 48) were randomly divided into four groups. To induce diabetes, two groups received low‐dose STZ and two groups served as controls. After diabetes induction, rosiglitazone (a PPARγ agonist) was administered by oral gavage to one of the diabetic and one of the non‐diabetic groups. Results: Rosiglitazone reduced significantly the atherosclerotic aortic plaque area in both diabetic and non‐diabetic apoE‐deficient mice: 340 ± 54 vs. 201 ± 27 μmol 2 (p = 0.001) in diabetic mice; 243 ± 22 vs. 158 ± 27 μmol 2 (p = 0.001) in non‐diabetic mice. Also, rosiglitazone reduced the correlation coefficient between plasma glucose and the degree of atherosclerosis (p < 0.0025) without affecting plasma glucose levels. The rosiglitazone‐treated mice, both diabetic and non‐diabetic, had higher lipid levels. Conclusions: Rosiglitazone‐treated animals showed less atherosclerosis despite higher lipid levels and similar glucose levels. These data suggest a direct anti‐atherogenic effect of rosiglitazone on the arterial wall.