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- Title
Effects of insulin sensitizers on plaque vulnerability associated with elevated lipid content in atheroma in ApoE-knockout mice.
- Authors
Cefalu, W. T.; Wang, Z. Q.; Schneider, D. J.; Absher, P. M.; Baldor, L. C.; Taatjes, D. J.; Sobel, B. E.
- Abstract
Acute coronary syndromes are generally precipitated by rupture of lipid-laden, relatively acellular, vulnerable atherosclerotic plaques with thin fibrous caps. We investigated whether a high-fat diet alters insulin sensitivity and whether insulin sensitizers (troglitazone and rosiglitazone) alter the composition of otherwise lipidladen atherosclerotic plaques in mice deficient in apolipoprotein E (ApoE). ApoE-knockout mice were fed a high-fat (n=30) or standard chow (n=10) diet for two weeks. Thereafter, those fed the high-fat diet were treated with troglitazone (n=10), rosiglitazone (n=10) or no drug (n=10) for 16 weeks beginning at 8 weeks of age. Carbohydrate metabolism was assessed with intraperitoneal glucose tolerance tests and insulin tolerance tests. Plaque composition was characterised with confocal laser scanning microscopy. The high-fat diet induced insulin resistance in the absence of weight gain. Compared with control animals on the high-fat diet, animals given troglitazone (400 mg/kg/day) or rosiglitazone (4 mg/kg/day) had significantly less area under the curve (AUC) for insulin (p<0.05) and glucose disposal (p<0.05). Despite significant increases in insulin sensitivity with drug treatment, no change in HDL-cholesterol and triglyceride levels, nor reduction in atheroma size or lipid content was noted. Thus, improvement in insulin resistance induced by a high-fat diet in this animal model of vasculopathy did not alter plaque composition.
- Subjects
INSULIN; LIPIDS; GLUCOSE; ATHEROSCLEROSIS; ATHEROSCLEROTIC plaque; DIABETES
- Publication
Acta Diabetologica, 2004, Vol 41, Issue 1, p25
- ISSN
0940-5429
- Publication type
Article
- DOI
10.1007/s00592-004-0140-4