Mita Tomoya, Otsuka Aiko, Azuma Kosuke, Uchida Toyoyoshi, Ogihara Takeshi, Fujitani Yoshio, Hirose Takahisa, Mitsumata Masako, Kawamori Ryuzo, Watada Hirotaka
Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Biochem Biophys Res Commun. 2007 Jul 6;358(3):679-85. doi: 10.1016/j.bbrc.2007.04.118. Epub 2007 May 4.
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.
本研究的目的是调查血糖水平波动对动脉粥样硬化形成的影响。将每天喂食两次麦芽糖的载脂蛋白（apo）E缺乏小鼠用作反复餐后血糖峰值的模型。我们研究了在给予和不给予α-葡萄糖苷酶抑制剂米格列醇的情况下，粘附于内皮的巨噬细胞数量和纤维化动脉粥样硬化病变的面积。通过免疫组织化学染色Mac-2后采用正面法对胸主动脉中巨噬细胞与内皮细胞的粘附进行定量，以便对内皮表面进行最佳观察。在弹性范吉森染色的主动脉近端测量动脉粥样硬化病变的面积。喂食麦芽糖开始后1周，粘附的巨噬细胞数量增加，喂食后5周，动脉粥样硬化病变大小增加。同时使用米格列醇可防止这些增加。我们的数据表明，血糖波动会加速动脉粥样硬化的形成。这与体内血清胆固醇水平的变化无关。α-葡萄糖苷酶抑制剂减少血糖波动可有效控制动脉粥样硬化的进展。
