Signaling pathways of kaempferol-3-neohesperidoside in glycogen synthesis in rat soleus muscle.

Kaempferol 3-neohesperidoside is one of the several compounds that have been reported to have insulin-like properties in terms of glucose lowering. We studied the effect of kaempferol 3-neohesperidoside in glycogen synthesis in rat soleus muscle through the incorporation of (14)C-d-glucose in glycogen. Kaempferol 3-neohesperidoside stimulates glycogen synthesis in rat soleus muscle by approximately 2.38-fold. Insulin at 100 nM showed a stimulatory effect on glycogen synthesis when compared with the control group. The stimulatory effect of kaempferol 3-neophesperidoside on glycogen synthesis was inhibited by wortmannin, the phosphatidylinositol 3-kinase (PI3K) inhibitor, and enhanced by lithium chloride, a glycogen synthase kinase 3 (GSK-3) inhibitor. Moreover, the stimulatory effect of kaempferol 3-neohesperidoside was also nullified by PD98059, a specific inhibitor of mitogen-activated protein kinase (MEK) and by calyculin A, an inhibitor of protein phosphatase 1 (PP1) activity. It was concluded that the PI3K - GSK-3 pathway and MAPK - PP1 pathway are involved in the stimulatory kaempferol 3-neohesperidoside effect on glycogen synthesis in rat soleus muscle.