TY - JOUR
T1 - Regulation by metformin of the hexose transport system in vascular endothelial and smooth muscle cells
AU - Sasson, Shlomo
AU - Gorowits, Naira
AU - Joost, Hans G.
AU - King, George L.
AU - Cerasi, Erol
AU - Kaiser, Nurit
PY - 1996
Y1 - 1996
N2 - 1. The effect of the biguanide metformin on hexose transport activity was studied in bovine cultured aortic endothelial (BEC) and smooth muscle cells (BSMC). 2. Metformin elevated the rate of hexose transport determined with 2-deoxyglucose (2DG) in a dose- and time-dependent manner in both cell types. Similar ED50 values (0.8-1.0 mM) were determined for the effect of metformin on 2DG uptake in both BEC and BSMC following 24 h exposure to increasing concentrations of metformin, with maximal stimulation at 2 mM. 3. In BEC, metformin increased the hexose transport 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 hexose transport ~ 2 fold. The drug was also effective at lower glucose levels, but did not exceed the maximal transport rate observed in glucose-deprived cells. 4. Similar results were obtained when the effect of metformin on hexose transport activity was assessed with the non-metabolizable hexose analogue, 3-O-methylglucose, suggesting that the drug affects primarily the rate of hexose transport rather than its subsequent phosphorylation. 5. The metformin-induced increase in hexose transport in BSMC treated for 24 h with the drug correlated with increased abundance of GLUT1 protein in the plasma membrane, as determined 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.
AB - 1. The effect of the biguanide metformin on hexose transport activity was studied in bovine cultured aortic endothelial (BEC) and smooth muscle cells (BSMC). 2. Metformin elevated the rate of hexose transport determined with 2-deoxyglucose (2DG) in a dose- and time-dependent manner in both cell types. Similar ED50 values (0.8-1.0 mM) were determined for the effect of metformin on 2DG uptake in both BEC and BSMC following 24 h exposure to increasing concentrations of metformin, with maximal stimulation at 2 mM. 3. In BEC, metformin increased the hexose transport 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 hexose transport ~ 2 fold. The drug was also effective at lower glucose levels, but did not exceed the maximal transport rate observed in glucose-deprived cells. 4. Similar results were obtained when the effect of metformin on hexose transport activity was assessed with the non-metabolizable hexose analogue, 3-O-methylglucose, suggesting that the drug affects primarily the rate of hexose transport rather than its subsequent phosphorylation. 5. The metformin-induced increase in hexose transport in BSMC treated for 24 h with the drug correlated with increased abundance of GLUT1 protein in the plasma membrane, as determined 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.
KW - Diabetes mellitus
KW - Glucose transporter
KW - Hexose transport
KW - Metformin
KW - Non-insulin dependent
KW - Vascular endothelium
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=0029867131&partnerID=8YFLogxK
U2 - 10.1111/j.1476-5381.1996.tb16731.x
DO - 10.1111/j.1476-5381.1996.tb16731.x
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C2 - 8882631
AN - SCOPUS:0029867131
SN - 0007-1188
VL - 117
SP - 1318
EP - 1324
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 6
ER -