REGULATION BY METFORMIN OF THE HEXOSE-TRANSPORT SYSTEM IN VASCULAR ENDOTHELIAL AND SMOOTH-MUSCLE CELLS

1 The effect of the biguanide metformin on hexose transport activity w as studied in bovine cultured aortic endothelial (BEG) and smooth musc le cells (BSMC).2 Metformin elevated the rate of hexose transport dete rmined with, 2-deoxyglucose (2DG) in a dose- and time-dependent manner in both cell types. Similar ED(50) values (0.8-1.0 mM) were determine d for the effect of metformin on 2DG uptake in both BEC and BSMC follo wing 24 h exposure to increasing concentrations of metformin, with max imal stimulation at 2 mM. 3 In BEG, metformin increased the hexose tra nsport rate 2-3 fold at all glucose concentrations tested (3.3-22.2 mM ). In BSMC incubated with 22.2 mM glucose, metformin elevated the hexo se transport similar to 2 fold. The drug was also effective at lower g lucose levels, but did not exceed the maximal transport rate observed in glucose-deprived cells. 4 Similar results were obtained when the ef fect of metformin on hexose transport activity was assessed with the n on-metabolizable hexose analogue, 3-O-methylglucose, suggesting that t he drug affects primarily the rate of hexose transport rather than its subsequent phosphorylation. 5 The metformin-induced increase in hexos e transport in BSMC treated for 24 h with the drug correlated with inc reased abundance of GLUT1 protein in the plasma membrane, as determine d by Western blot analysis. 6 These data indicate that in addition to its known effects on hexose metabolism in insulin responsive tissues, metformin also affects the hexose transport system in vascular cells. This may contribute to its blood glucose lowering capacity in patients with Type 2, non-insulin-dependent diabetes mellitus.