title: Swings in blood glucose levels accelerate atherogenesis in apolipoprotein E-deficient mice.
abstract: The aim of this study was to investigate the effect of fluctuations in blood glucose levels on atherogenesis. Apolipoprotein (apo) E-deficient mice fed maltose twice daily were used as a model of repetitive postprandial glucose spikes. We investigated the number of macrophages adherent to the endothelium and the area of fibrotic arteriosclerotic lesions, with and without administration of miglitol, an alpha-glucosidase inhibitor. Macrophage adhesion to endothelial cells in thoracic aorta was quantitated by the en face method for optimal observation of endothelial surface after immunohistochemical staining for Mac-2. The area of arteriosclerotic lesions was measured in elastica van Giesson-stained proximal aorta. The number of adherent macrophages increased at 1 week after commencement of maltose feeding and the size of arteriosclerotic lesion increased at 5 weeks after such feeding. These increases were prevented by simultaneous use of miglitol. Our data demonstrated that glucose fluctuations accelerate atherogenesis. This was independent of changes in serum cholesterol level in vivo. Reduction of glucose fluctuation by alpha-glucosidase inhibitor efficiently controlled the progression of atherosclerosis.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Mita
authors.forename: Aiko
authors.initials: A
authors.lastname: Otsuka
authors.forename: Kosuke
authors.initials: K
authors.lastname: Azuma
authors.forename: Toyoyoshi
authors.initials: T
authors.lastname: Uchida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogihara
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Masako
authors.initials: M
authors.lastname: Mitsumata
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D001161:Arteriosclerosis / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood*; D001786:Blood Glucose; D002318:Cardiovascular Diseases / Q000378:metabolism; D002448:Cell Adhesion; D002784:Cholesterol / Q000097:blood; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008320:Maltose / Q000378:metabolism; D051379:Mice
chemical_list: D001057:Apolipoproteins E; D001786:Blood Glucose; D008320:Maltose; D002784:Cholesterol; D005947:Glucose