Acute Kaempferol Stimulation Induces AKT Phosphorylation in HepG2 Cells

Abstract

Type 2 diabetes mellitus (T2DM) stands as a prevalent global public health issue caused by deficiencies in the action of insulin and/or insulin production. In the liver, insulin plays an important role by inhibiting hepatic glucose production and stimulating glycogen storage, thereby contributing to blood glucose regulation. Kaempferitrin (KP) and kaempferol (KM), flavonoids found in Bauhinia forficata, exhibit insulin-mimetic properties, showing promise in managing T2DM. In this study, we aimed to assess the potential of these compounds in modulating the insulin signaling pathway and/or glucose metabolism. Cell viability assays confirmed the non-cytotoxic nature of both compounds toward HepG2 cells at the concentrations and times evaluated. Theoretical molecular docking studies revealed that KM had the best docking pose with the IR β subunit when compared to the KP. Moreover, Langmuir monolayer evaluation indicated molecular incorporation for both KM and KP. Specifically, KM exhibited the capability to increase AKT phosphorylation, a key kinase in insulin signaling, regardless of insulin receptor (IR) activation. Notably, KM showed an additional synergistic effect with insulin in activating AKT. In conclusion, our findings suggest the potential of KM as a promising compound for stimulating AKT activation, thereby influencing energy metabolism in T2DM.

Keywords

• type 2 diabetes mellitus
• flavonoids
• insulin signaling
• liver cells