Oxidovanadium(IV) sulfate-induced glucose uptake in HepG2 cells through IR/Akt pathway and hydroxyl radicals

•VOSO4 enhances glucose uptake in HepG2 cells.•VOSO4 increases IR and Akt phosphorylation in HepG2 cells.•VOSO4 triggers increase in intracellular reactive oxygen species (ROS) generation.•·OH may be involved in activation of IR/Akt signaling pathway for glucose uptake caused by VOSO4.

The insulin-mimetic and anti-diabetic properties of vanadium and related compounds have been well documented both in vitro and in vivo. However, the molecular basis of the link between vanadium and the insulin signaling pathway in diabetes mellitus is not fully described. We investigated the effects of reactive oxygen species (ROS) induced by oxidovanadium(IV) sulfate (VOSO4) on glucose uptake and the insulin signaling pathway in human hepatoma cell line HepG2. Exposure of cells to VOSO4 (5–50 μM) resulted in an increase in glucose uptake, insulin receptor (IR) and protein kinase B (Akt) phosphorylation and intracellular ROS generation. Using Western blot, we found that catalase and sodium formate, but not superoxide dismutase, prevented the increase of hydroxyl radical (·OH) generation and significantly decreased VOSO4-induced IR and Akt phosphorylation. These results suggest that VOSO4-induced ·OH radical, which is a signaling species, promotes glucose uptake via the IR/Akt signaling pathway.

Graphical abstractVanadium compounds with various oxidation states have different anti-diabetic effects due to vanadium-mediated generation of ROS as signaling molecules to activate cellular stress-sensitive signaling pathways.Figure optionsDownload full-size imageDownload as PowerPoint slide