Department of Applied Life Science, Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509, Japan.
Eur J Nutr. 2013 Sep;52(6):1607-19. doi: 10.1007/s00394-012-0466-6. Epub 2012 Dec 13.
Although several researches have demonstrated that rooibos extract has hypoglycemic effect, the role of aspalathin, a main polyphenol in the extract, remains unclear. Our aims were to find specific mechanisms for anti-diabetic action of aspalathin employing a rat skeletal muscle-derived cell line (L6 myocytes) and a rat-derived pancreatic β-cell line (RIN-5F cells) and to investigate its effect in type 2 diabetic model ob/ob mice.
We investigated in vitro the effect of aspalathin on the glucose metabolism through the studies on molecular mechanisms of glucose uptake using cultured L6 myotubes. We also measured the antioxidative ability of aspalathin against reactive oxygen species (ROS) generated by artificial advanced glycation end product (AGE) in RIN-5F cells. In vivo, ob/ob mice were fed 0.1 % aspalathin-containing diet for 5 weeks, and the effect of aspalathin on fasting blood glucose level, glucose intolerance, and hepatic gene expression was studied.
Aspalathin dose dependently increased glucose uptake by L6 myotubes and promoted AMP-activated protein kinase (AMPK) phosphorylation. Aspalathin enhanced GLUT4 translocation to plasma membrane in L6 myoblasts and myotubes. In RIN-5F cells, aspalathin suppressed AGE-induced rises in ROS. In vivo, aspalathin significantly suppressed the increase in fasting blood glucose levels and improved glucose intolerance. Furthermore, aspalathin decreased expression of hepatic genes related to gluconeogenesis and lipogenesis.
Hypoglycemic effect of aspalathin is related to increased GLUT4 translocation to plasma membrane via AMPK activation. In addition, aspalathin reduces the gene expression of hepatic enzymes related to glucose production and lipogenesis. These results strongly suggest that aspalathin has anti-diabetic potential.
尽管已有多项研究表明南非路易波士茶提取物具有降血糖作用，但该提取物中的主要多酚化合物——Aspalathin 的作用机制尚不清楚。本研究旨在利用大鼠骨骼肌衍生细胞系（L6 肌母细胞）和大鼠胰岛β细胞系（RIN-5F 细胞）寻找 Aspalathin 抗糖尿病作用的具体机制，并在 2 型糖尿病 ob/ob 小鼠模型中研究其作用。
我们通过研究培养的 L6 肌管细胞葡萄糖摄取的分子机制，研究了 Aspalathin 对葡萄糖代谢的体外影响。我们还测量了 Aspalathin 对由人工糖基化终产物（AGE）产生的活性氧（ROS）的抗氧化能力在 RIN-5F 细胞中的作用。在体内，ob/ob 小鼠喂食含 0.1% Aspalathin 的饮食 5 周，研究了 Aspalathin 对空腹血糖水平、葡萄糖耐量和肝基因表达的影响。
Aspalathin 呈剂量依赖性增加 L6 肌管细胞的葡萄糖摄取，并促进 AMP 激活蛋白激酶（AMPK）磷酸化。Aspalathin 增强了 L6 成肌细胞和肌管细胞中 GLUT4 向质膜的转位。在 RIN-5F 细胞中，Aspalathin 抑制了 AGE 诱导的 ROS 升高。在体内，Aspalathin 显著抑制了空腹血糖水平的升高，并改善了葡萄糖耐量。此外，Aspalathin 降低了与糖异生和脂肪生成相关的肝基因表达。
Aspalathin 的降血糖作用与其通过 AMPK 激活增加 GLUT4 向质膜的转位有关。此外，Aspalathin 降低了与葡萄糖生成和脂肪生成相关的肝酶基因表达。这些结果强烈表明 Aspalathin 具有抗糖尿病潜力。
