Shuto Yuki, Asai Akira, Nagao Mototsugu, Sugihara Hitoshi, Oikawa Shinichi
Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
PLoS One. 2015 Aug 27;10(8):e0136840. doi: 10.1371/journal.pone.0136840. eCollection 2015.
A number of epidemiological studies demonstrated that postprandial hyperglycemia is a risk factor for cardiovascular disease in individuals with impaired glucose tolerance. Although several laboratory studies have addressed the plausible causal role of postprandial acute hyperglycemia (glucose spikes) in the development of atherosclerosis, there is little convincing evidence in vivo whether the atherosclerotic lesion formation can be accelerated solely by glucose spikes. Here, we assessed the effect of repetitive glucose spikes on atherosclerotic lesion formation in mice.
Female C57BL/6 mice were fed an atherogenic diet from 8 to 28 weeks of age. During the atherogenic diet feeding period, the mice orally received a glucose solution (50 mg glucose/mouse; G group) or water (W group) twice daily, 6 days a week. Atherosclerotic lesion formation in the aortic sinus was quantitatively analyzed in serial cross-sections by oil red O staining.
G group mice showed transient increases in blood glucose level (~5 mmol/L above W group), and the levels returned to levels similar to those in W group mice within 60 min. No significant differences in glucose tolerance, insulin sensitivity, and plasma lipid profiles were observed after the 20-week repetitive administration between the 2 groups. G group mice showed an approximately 4-fold greater atherosclerotic lesion size in the aortic sinus than W group mice. Gene expression levels of Cd68 and Icam1 in the thoracic aorta were higher in G group mice than in W group mice.
These results indicate that glucose spikes can accelerate atherosclerotic lesion formation, with little influence on other metabolic disorders. Repetitive glucose administration in wild-type mice may serve as a simple and useful approach to better understanding the causal role of glycemic spikes in the development of atherosclerosis.
多项流行病学研究表明，餐后高血糖是糖耐量受损个体发生心血管疾病的危险因素。尽管一些实验室研究探讨了餐后急性高血糖（血糖峰值）在动脉粥样硬化发生发展中可能的因果作用，但在体内几乎没有令人信服的证据表明仅血糖峰值就能加速动脉粥样硬化病变的形成。在此，我们评估了重复性血糖峰值对小鼠动脉粥样硬化病变形成的影响。
雌性C57BL/6小鼠在8至28周龄期间喂食致动脉粥样硬化饮食。在致动脉粥样硬化饮食喂养期间，小鼠每天口服葡萄糖溶液（50毫克葡萄糖/只；G组）或水（W组）两次，每周6天。通过油红O染色对主动脉窦的动脉粥样硬化病变形成进行连续横断面定量分析。
G组小鼠血糖水平出现短暂升高（比W组高约5 mmol/L），且在60分钟内恢复到与W组小鼠相似的水平。两组在20周重复给药后，葡萄糖耐量、胰岛素敏感性和血浆脂质谱均未观察到显著差异。G组小鼠主动脉窦的动脉粥样硬化病变大小比W组小鼠大近4倍。G组小鼠胸主动脉中Cd68和Icam1的基因表达水平高于W组小鼠。
这些结果表明，血糖峰值可加速动脉粥样硬化病变形成，对其他代谢紊乱影响较小。在野生型小鼠中重复给予葡萄糖可能是一种简单而有用的方法，有助于更好地理解血糖峰值在动脉粥样硬化发生发展中的因果作用。
