Abstract
Activation of phosphatidylinositol 3-kinase (PI3K) by insulin is necessary for the effect of insulin to recruit GLUT4 to the cell surface in insulin target cells. In adipose cells, stimulation of endogenous PDGF receptors (PDGF-R) results in increased PI3K activity without causing recruitment of GLUT4. We overexpressed wild-type or mutant forms of the PDGF-R in rat adipose cells and examined their effects on PDGF- and insulin-stimulated recruitment of co-transfected epitope-tagged GLUT4. Control cells expressing only tagged GLUT4 had a 3-fold increase in cell surface GLUT4 upon insulin stimulation but no response to PDGF. Cells overexpressing wild-type PDGF-R maintained insulin responsiveness and, in addition, acquired the ability to recruit GLUT4 in response to PDGF. Surprisingly, overexpression of F740/ F751 (mutant PDGF-R unable to directly activate PI3K) led to similar results. Nevertheless, wortmannin (an inhibitor of PI3K) blocked effects of both PDGF and insulin to recruit GLUT4. Our data suggest that overexpression of PDGF-R mediates positive effects on GLUT4 translocation by a wortmannin sensitive pathway not dependent on direct interaction of the PDGF-R with PI3K.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adipose Tissue / metabolism*
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Animals
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Cell Membrane / metabolism
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Cloning, Molecular
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Epididymis
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Epitopes
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Glucose Transporter Type 4
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Humans
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Insulin / pharmacology
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Male
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Monosaccharide Transport Proteins / biosynthesis
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Monosaccharide Transport Proteins / metabolism*
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Muscle Proteins*
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Mutagenesis, Site-Directed
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Phosphatidylinositol 3-Kinases
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Platelet-Derived Growth Factor / metabolism
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Platelet-Derived Growth Factor / pharmacology*
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Point Mutation
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Protein Processing, Post-Translational
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Rats
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor / biosynthesis
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Receptors, Platelet-Derived Growth Factor / physiology*
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Recombinant Proteins / metabolism
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Sequence Tagged Sites
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Transfection
Substances
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Epitopes
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Glucose Transporter Type 4
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Insulin
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Monosaccharide Transport Proteins
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Muscle Proteins
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Platelet-Derived Growth Factor
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Recombinant Proteins
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SLC2A4 protein, human
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Slc2a4 protein, rat
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Receptor, Platelet-Derived Growth Factor beta
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Receptors, Platelet-Derived Growth Factor