Phenolic compounds ameliorate the glucose uptake in HepG2 cells' insulin resistance via activating AMPK

• Phenolics protect HepG2 functionality by regulating glycogen content. • Phenolics protect HepG2 functionality by modulating glucose production and uptake. • AM and DA restrain the inhibition of AKT and AMPK caused by high glucose. The preventive effects of phenolic compounds on insulin signalling and on both glucose production and uptake were studied in insulin-responsive human HepG2 cells treated with high glucose. The influence of insulin in different-dose insulin and at different action times on the IR of HepG2 cells, and changes of glucose uptake and glycogen level were detected by using cell culture glucose uptake analysis. Seven compounds, agrimonolide ( 1 ), desmethylagrimonolide ( 2 ), quercetin ( 3 ), luteolin ( 4 ), luteolin- 7 - O -glucoside ( 5 ), kaempferol ( 6 ), and apigenin ( 7 ), were used. The IR model was successfully established in HepG2 cells after the action of 5 × 10 −7 M insulin for 24 h. The analysis of glucose uptake showed that 1–3 samples had significant glucose lowering activity and exhibited no difference with metformin ( P > 0.05). All compounds had low cytotoxicity in HepG2 cells within the test concentration. Compounds 1 and 2 pre-treatment also prevented the inactivation of the AKT pathway and AMPK, which play an important role in glycometabolism.