Food Certification Center, Korean Food Research Institutes, Sungnam, South Korea.
J Nutr. 2013 Jul;143(7):1093-9. doi: 10.3945/jn.112.173401. Epub 2013 May 29.
Our preliminary study revealed that dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis (unpublished). We therefore evaluated whether long-term oral consumption of yuzu (Citrus junos Tanaka) extract improves cognitive dysfunction and glucose homeostasis in β-amyloid-induced rats. Male rats received hippocampal CA1 infusions of β-amyloid (25-35) [plaque forming β-amyloid; Alzheimer disease (AD)] or β-amyloid (35-25) [non-plaque forming β-amyloid; C (non-Alzheimer disease control)] at a rate of 3.6 nmol/d for 14 d. AD rats were divided into 2 dietary groups that received either 3% lyophilized 70% ethanol extracts of yuzu (AD-Y) or 3% dextrin (AD-C) in high-fat diets (43% energy as fat). The AD-C group exhibited greater hippocampal β-amyloid deposition, which was not detected in the C group, and attenuated hippocampal insulin signaling. Yuzu treatment prevented β-amyloid accumulation, increased tau phosphorylation, and attenuated hippocampal insulin signaling observed in AD-C rats. Consistent with β-amyloid accumulation, the AD-C rats experienced cognitive dysfunction, which was prevented by yuzu. AD-C rats gained less weight than did C rats due to decreased feed consumption, and yuzu treatment prevented the decrease in feed consumption. Serum glucose concentrations were higher in AD-C than in C rats at 40-120 min after glucose loading during an oral-glucose-tolerance test, but not at 0-40 min. Serum insulin concentrations were highly elevated in AD-C rats but not enough to lower serum glucose to normal concentrations, indicating that rats in the AD-C group had insulin resistance and a borderline diabetic state. Although AD-C rats were profoundly insulin resistant, AD-Y rats exhibited normal first and second phases of glucose tolerance and insulin sensitivity and secretion. In conclusion, yuzu treatment prevented the cognitive dysfunction and impaired energy and glucose homeostasis induced by β-amyloid infusion.
我们的初步研究表明，β-淀粉样蛋白积累引起的痴呆症会损害外周葡萄糖稳态（未发表）。因此，我们评估了长期口服柚子（Citrus junos Tanaka）提取物是否能改善β-淀粉样蛋白诱导的大鼠的认知功能障碍和葡萄糖稳态。雄性大鼠以 3.6 nmol/d 的速度接受海马 CA1 内β-淀粉样蛋白（25-35）[斑块形成β-淀粉样蛋白；阿尔茨海默病（AD）]或β-淀粉样蛋白（35-25）[非斑块形成β-淀粉样蛋白；C（非阿尔茨海默病对照）]共 14 天。AD 大鼠分为 2 个饮食组，分别给予高脂肪饮食（43%能量为脂肪）中的 3%冻干 70%乙醇柚子提取物（AD-Y）或 3%糊精（AD-C）。AD-C 组表现出更大的海马β-淀粉样蛋白沉积，而 C 组未检测到，并且海马胰岛素信号减弱。柚子处理可防止 AD-C 大鼠中观察到的β-淀粉样蛋白积聚、tau 磷酸化增加和海马胰岛素信号减弱。与β-淀粉样蛋白积聚一致，AD-C 大鼠出现认知功能障碍，柚子可预防。AD-C 大鼠的体重增长低于 C 大鼠，因为饲料摄入量减少，而柚子处理可防止饲料摄入量减少。口服葡萄糖耐量试验中，AD-C 大鼠在葡萄糖负荷后 40-120 分钟时的血清葡萄糖浓度高于 C 大鼠，但在 0-40 分钟时没有差异。AD-C 大鼠的血清胰岛素浓度显著升高，但不足以将血清葡萄糖降低至正常浓度，表明 AD-C 组大鼠存在胰岛素抵抗和边缘糖尿病状态。尽管 AD-C 大鼠存在严重的胰岛素抵抗，但 AD-Y 大鼠表现出正常的第一和第二阶段葡萄糖耐量和胰岛素敏感性和分泌。总之，柚子处理可预防β-淀粉样蛋白输注引起的认知功能障碍和能量及葡萄糖稳态受损。
