The Journal of Japan Atherosclerosis Society
Online ISSN : 2185-8284
Print ISSN : 0386-2682
ISSN-L : 0386-2682
Studies on Genetically Obese Zucker Fatty Rats Part II:Significance of Hyperinsulinism on Development of the Aortic Lesions
Tomoyoshi HOSOKAWAKeiji NISHIYAMAYukio KISHIKentaro SHIMOKADOTadayoshi KOYAMAAkira TANAKAIsao UCHIMURATomoe KUROIWAGakuzo TAMURAFujio NUMANO
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1988 Volume 16 Issue 1 Pages 63-72

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Abstract

It has been reported by Stout et al, that hyperinsulinism might accelerate atherosclerosis. In the Zucker rat strain, made by Zucker and Zucker in 1961, the presence of the “fa” gene in the homozygous condition (fa/fa) leads to the development of hyperinsulinism of early onset.
In order to investigate how hyperinsulinism causes atherosclerosis, age-related changes in the aortic lesions were studied in Zucker fatty rats (fatty rat) and their lean littermates (lean rat) at 7, 11, 20 weeks of age. Serum glucose, cholesterol and triglyceride concentration were determined using enzymatic methods. Cholesterol contents in the aorta were analyzed by the Gas Liquid Chromatography. Morphological studies were performed light and electromicroscopically in the aorta of rats.
The following results were obtained;
1. The fatty rats showed a remarkable increase in the body weight with age.
2. The levels of serum triglyceride and cholesterol of the fatty rats were higher than those of the lean rats at the same age. But there was no significant difference in serum glucose level between the fatty rats and the lean rats at 7, 11, 20 weeks of age.
3. At 20 weeks of age, cholesterol content in the aorta of the fatty rats was significantly higher than that of the lean rats. Triglyceride content in the aorta of the fatty rats was higher than that of the lean rats at 11 weeks of age.
4. The aorta and serum of the fatty rats contained significantly higher amount of nonessential fatty acids (C16, C16-1, C18-1) with a concomitant decrease in C18-2, C20-4 as compared with those in the lean rats.
5. The light microscopic examination revealed slight thickening of the intima of the aorta due to increase both in cellular components and matrixes in the fatty rats of 20 weeks of age. Electron microscopic observations demonstrated the accumulation of homogeneous substances and smooth musclelike cells in the intima of 20 weeks old fatty rats. The aorta of the lean rats was almost normal by light and electro microscopy.
These data suggest that hyperinsulinism plays an important role in development of diabetic macroangiopathy.

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