Universidade Federal da Fronteira Sul, Campus Universitário Laranjeiras do Sul, Bairro Vila Alberti, CEP 85303-775, Laranjeiras do Sul, PR, Brazil.
Eur J Pharmacol. 2013 Jul 15;712(1-3):1-7. doi: 10.1016/j.ejphar.2013.02.029. Epub 2013 Mar 1.
The aim of the study was to investigate the in vitro effect and the mechanism of action of kaempferitrin on glucose uptake in an insulin target (soleus muscle). A stimulatory effect of kaempferitrin on glucose uptake was observed when rat soleus muscle was incubated with 10, 100 and 1000 ηM of this flavonoid glycoside. The presence of specific insulin signaling inhibitors, such as wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, an inhibitor of mitogen-activated protein kinase (MEK), HNMPA(AM)3, an insulin receptor tyrosine kinase activity inhibitor, colchicine, a microtubule-depolymerizing agent, SB239063, an inhibitor of P38 MAPK and cycloheximide, an inhibitor of protein synthesis showed that kaempferitrin triggers different metabolic and nuclear pathways in skeletal muscle. Besides the influence on glycogen storage, the metabolic action involves the insulin receptor, PI3K, atypical PKC activity and the translocation of GLUT4. Additionally, the nuclear pathways (via MAPK and MEK) provide evidence of the stimulation of the expression of glucose transporters or other signaling proteins, reinforcing proposals that skeletal muscle represents a primary site at which kaempferitrin exerts its effect promoting glucose homeostasis. Also, these similarities with the signaling pathways of insulin constitute strong evidence for the insulin-mimetic role of kaempferitrin in glucose homeostasis.
本研究旨在探讨山柰酚-3-O-芸香糖苷（一种类黄酮糖苷）在体外对葡萄糖摄取的作用及其作用机制。当用 10、100 和 1000 ηM 的山柰酚-3-O-芸香糖苷孵育大鼠比目鱼肌时，观察到其对葡萄糖摄取有刺激作用。特异性胰岛素信号抑制剂，如磷酸肌醇 3-激酶（PI3K）抑制剂wortmannin、蛋白激酶 C（PKC）抑制剂 RO318220、丝裂原活化蛋白激酶（MEK）抑制剂 PD98059、胰岛素受体酪氨酸激酶活性抑制剂 HNMPA(AM)3、微管解聚剂秋水仙碱、P38 MAPK 抑制剂 SB239063 和蛋白合成抑制剂环己酰亚胺的存在表明，山柰酚-3-O-芸香糖苷在骨骼肌中触发不同的代谢和核途径。除了对糖原储存的影响外，代谢作用还涉及胰岛素受体、PI3K、非典型 PKC 活性和 GLUT4 的易位。此外，核途径（通过 MAPK 和 MEK）提供了刺激葡萄糖转运蛋白或其他信号蛋白表达的证据，这进一步证明了骨骼肌是山柰酚-3-O-芸香糖苷发挥其促进葡萄糖稳态作用的主要部位。此外，山柰酚-3-O-芸香糖苷在葡萄糖稳态中的胰岛素模拟作用与胰岛素信号通路具有很强的相似性，这也为其提供了有力证据。
