Involvement of phosphatidylinositol 3-kinase in stimulation of glucose transport by growth factors in 3T3-L1 adipocytes.
Activation of phosphatidylinositol 3-kinase (PI 3-kinase) appears to be part of the signaling mechanism by which insulin stimulates cellular glucose uptake. We have investigated the involvement of PI 3-kinase in the regulation of glucose uptake in 3T#-L1 adipocytes by comparing the effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and insulin. Stimulation of [14C]deoxyglucose uptake by PDGF and EGF was 29% and 70%, respectively, while that by insulin was 5-fold. Wortmannin, a PI 3-kinase inhibitor, completely blocked the effects of all three agonists. The relative effects of the growth factors on phosphatidlyinositoltriphosphate (PIP3) synthesis were also determined. Insulin caused a large increase in this phosphoinositide. The effect of PDGF was much smaller, in fact barely detectable, while EGF had no detectable effect. The results suggest a role for PI 3-kinase in stimulation of glucose uptake by PDGF and EGF. However, the degree of PI 3-kinase by these growth factors appears to be much smaller than that by insulin, consistent with smaller stimulations of glucose transport.
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K M
KM
Department of Cardiovascular Diseases Research, Searle Research and Development, St. Louis, MO 63167, USA.
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D006133:Growth Substances; D007328:Insulin; D018129:Phosphatidylinositol Phosphates; D010982:Platelet-Derived Growth Factor; C060974:phosphatidylinositol 3,4,5-triphosphate; D004815:Epidermal Growth Factor; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005947:Glucose; D000077191:Wortmannin