Differential regulation of glucose transport and glucose transporter (GLUT-1) gene expression by vanadate, phorbol ester and okadaic acid in L6 skeletal muscle cells.
Vanadate, an inhibitor of protein tyrosine phosphatases (PTPases), elicited time-and-dose-dependent increases in glucose transport in rat muscle L6 cells in culture: the rate was increased by 150-175% over control in 24 h at 75-100 microM. In contrast, molybdate, another inhibitor of PTPases, failed to stimulate glucose transport. The effect of vanadate was not blocked by tyrosine kinase inhibitors, genistein or tyrphostin RG 50864, implying that tyrosine kinase activation may not mediate the action of vanadate. The ability of vanadate to stimulate glucose transport was preserved in cells whose protein kinase C (PKC) activity was down-regulated by prior exposure to phorbol esters (TPA), suggesting that the vanadate effect was unrelated to the TPA-sensitive PKC isoform(s). Okadaic acid, an inhibitor of protein phosphatases 1 and 2A, was a potent activator of glucose transport increasing the rate 7-fold in 24 h at a concentration of 50 nM. The increases in GLUT-1 mRNA level in response to vanadate and TPA were paralleled bh much smaller increases in immunoreactive GLUT-1 protein level, whereas okadaic acid treatment markedly elevated GLUT-1 protein without a concomitant change in GLUT-1 mRNA levels.
Venkatesan
N
N
Research Institute, Cedars-Siani Medical Center-UCLA 90048, USA.
Davidson
M B
MB
D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D019319:Okadaic Acid; D010703:Phorbol Esters / Q000494:pharmacology*; D051381:Rats; D014638:Vanadates / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D004988:Ethers, Cyclic; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D010703:Phorbol Esters; C495679:Slc2a1 protein, rat; D019319:Okadaic Acid; D014638:Vanadates; D005947:Glucose