Department of Biochemistry, University of Maringá, Brazil.
Cell Biochem Funct. 2010 Mar;28(2):149-58. doi: 10.1002/cbf.1635.
Fisetin is a flavonoid dietary ingredient found in the smoke tree (Cotinus coggyria) and in several fruits and vegetables. The effects of fisetin on glucose metabolism in the isolated perfused rat liver and some glucose-regulating enzymatic activities were investigated. Fisetin inhibited glucose, lactate, and pyruvate release from endogenous glycogen. Maximal inhibitions of glycogenolysis (49%) and glycolysis (59%) were obtained with the concentration of 200 microM. The glycogenolytic effects of glucagon and dinitrophenol were suppressed by fisetin 300 microM. No significant changes in the cellular contents of AMP, ADP, and ATP were found. Fisetin increased the cellular content of glucose 6-phosphate and inhibited the glucose 6-phosphatase activity. Gluconeogenesis from lactate and pyruvate or fructose was inhibited by fisetin 300 microM. Pyruvate carboxylation in isolated intact mitochondria was inhibited (IC(50) = 163.10 +/- 12.28 microM); no such effect was observed in freeze-thawing disrupted mitochondria. It was concluded that fisetin inhibits glucose release from the livers in both fed and fasted conditions. The inhibition of pyruvate transport into the mitochondria and the reduction of the cytosolic NADH-NAD(+) potential redox could be the causes of the gluconeogenesis inhibition. Fisetin could also prevent hyperglycemia by decreasing glycogen breakdown or blocking the glycogenolytic action of hormones.
漆黄素是一种类黄酮膳食成分，存在于烟树（黄栌）和几种水果和蔬菜中。本文研究了漆黄素对离体灌注大鼠肝脏葡萄糖代谢和一些葡萄糖调节酶活性的影响。漆黄素抑制内源性肝糖原分解为葡萄糖、乳酸和丙酮酸。200μM 浓度时，最大抑制糖原分解（49%）和糖酵解（59%）。300μM 漆黄素抑制胰高血糖素和二硝基苯酚的糖原分解作用。细胞内 AMP、ADP 和 ATP 的含量没有明显变化。漆黄素增加了葡萄糖 6-磷酸的细胞内含量并抑制了葡萄糖 6-磷酸酶的活性。300μM 漆黄素抑制了从乳酸和丙酮酸或果糖的糖异生。300μM 漆黄素抑制了分离完整线粒体中的丙酮酸羧化作用（IC50=163.10±12.28μM）；在冻融破坏的线粒体中未观察到这种作用。结论是，漆黄素抑制了进食和禁食状态下肝脏中葡萄糖的释放。丙酮酸向线粒体的转运抑制和细胞质中 NADH-NAD+还原电势的降低可能是糖异生抑制的原因。漆黄素还可以通过减少肝糖原分解或阻断激素的糖原分解作用来预防高血糖。
