Growth factor-induced stimulation of hexose transport in 3T3-L1 adipocytes: evidence that insulin-induced translocation of GLUT4 is independent of activation of MAP kinase.
We have examined the effect of growth factors on the rate of hexose transport in 3T3-L1 adipocytes. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were found to stimulate deoxyglucose transport by about 2-fold. The concentrations of EGF and PDGF which elicited half maximal responses were 100 and 350 pM, respectively. The increases in transport rate were acute effects; the stimulations were evident within minutes of exposure to growth factors. By contrast, insulin stimulated deoxyglucose transport approximately 16-fold over similar time periods. We have measured the appearance of both the insulin-responsive glucose transporter (GLUT4) and the erythrocyte-type glucose transporter (GLUT1) at the cell surface in response to insulin, EGF and PDGF. We show that both EGF and PDGF induce a 2-fold increase in GLUT1 at the cell surface, but both these growth factors were without effect on GLUT4 levels at the cell surface. In contrast, insulin induced a 13-fold increase in cell surface GLUT4. We further show that insulin, EGF and PDGF all activate MAP kinase as determined by a shift in electrophoretic mobility of this protein on SDS-PAGE. However, since the large translocation of GLUT4 to the cell surface is specific for insulin, we suggest that activation of MAP kinase is not the sole requisite for this process.
Gould
G W
GW
Department of Biochemistry, University of Glasgow, UK.
Merrall
N W
NW
Martin
S
S
Jess
T J
TJ
Campbell
I W
IW
Calderhead
D M
DM
Gibbs
E M
EM
Holman
G D
GD
Plevin
R J
RJ
D016475:3T3 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006133:Growth Substances; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D003847:Deoxyglucose; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1