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.
Department of Cardiovascular Diseases Research, Searle Research and Development, St. Louis, MO 63167, USA.
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Conricode
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