Mitogen-activated protein kinase activation is not sufficient for stimulation of glucose transport or glycogen synthase in 3T3-L1 adipocytes.
The role of mitogen-activated protein (MAP) kinase in the regulation of glucose metabolism has been investigated by comparing the effects of insulin and epidermal growth factor (EGF) on MAP kinase activation, glucose transport, and glycogen synthase in 3T3-L1 adipocytes. Insulin or EGF treatment for 5 min increased p42mapk and p44mapk activity to the same extent as determined by myelin basic protein kinase activity measurements and phosphotyrosine immunoblotting. The profiles of myelin basic protein kinase activity following MonoQ chromatography of extracts obtained from cells incubated with insulin or EGF were almost identical. Insulin increased glucose transport and GLUT4 translocation to the cell surface by 15- and 7-fold, respectively. EGF had no significant effect on these processes. Insulin increased the glycogen synthase ratio (-Glc-6-P/+Glc-6-P) by 7.5- and 3.5-fold in the presence and absence of glucose, respectively. EGF increased the ratios by only 2- and 1.3-fold, respectively. EGF did not appear to inhibit downstream of MAP kinase, because when adipocytes were incubated with insulin plus EGF, the stimulation of glucose transport and glycogen synthase was similar to that observed with insulin alone. These findings indicate that activation of the MAP kinase isoforms p42mapk and p44mapk is not sufficient for the activation of glucose transport and glycogen synthase in 3T3-L1 adipocytes.
Robinson
L J
LJ
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110.
Razzack
Z F
ZF
Lawrence
J C
JC
James
D E
DE
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D006006:Glycogen Synthase / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D004815:Epidermal Growth Factor; D006006:Glycogen Synthase; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D038362:Glycogen Synthase Kinase 3; D005947:Glucose