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J. Biol. Chem., Vol. 266, Issue 4, 2615-2621, 02, 1991
UM Koivisto, H Martinez-Valdez, PJ Bilan, E Burdett, T Ramlal and A Klip
The regulation by glucose and insulin of the muscle-specific facilitative
glucose transport system GLUT-4 was investigated in L6 muscle cells in
culture. Hexose transport activity, mRNA expression, and the subcellular
localization of the GLUT-4 protein were analyzed. As observed previously
(Walker, P. S., Ramlal, T., Sarabia, V., Koivisto, U.-M., Bilan, P. J.,
Pessin, J. E., and Klip, A. (1990) J. Biol. Chem. 265, 1516-1523), 24 h of
glucose starvation and 24 h of insulin treatment each increase glucose
transport activity severalfold. Here we report a differential regulation of
the GLUT-4 and GLUT-1 transport systems under these conditions. (a) The
level of GLUT-4 mRNA was not affected by glucose starvation and was
diminished by prolonged (24 h) administration of insulin; in contrast, the
level of GLUT-1 mRNA was elevated under both conditions. (b) Glucose
starvation and prolonged insulin administration increased the amount of
both GLUT-4 and GLUT-1 proteins in the plasma membrane. (c) In
intracellular membranes, glucose starvation elevated, and prolonged insulin
administration reduced, the GLUT-4 protein content. In contrast, the GLUT-1
protein content in these membranes decreased with glucose starvation and
increased with insulin treatment. Glucose transport was rapidly curbed upon
refeeding glucose to glucose-starved cells, with half-maximal reversal
after 30 min and maximal reversal after 4 h. This was followed by a marked
decrease in the levels of GLUT-1 mRNA without major changes in GLUT-4 mRNA.
Neither 2-deoxy-D-glucose nor 3-O-methyl- D-glucose could substitute for
D-glucose in these effects. It is proposed that glucose and insulin
differentially regulate the two glucose transport systems in L6 muscle
cells and that the rapid down- regulation of hexose transport activity by
glucose is regulated by post- translational mechanisms.
Differential regulation of the GLUT-1 and GLUT-4 glucose transport systems by glucose and insulin in L6 muscle cells in culture
Department of Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
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