title: Mechanism of IGF-I-stimulated glucose transport in human adipocytes. Demonstration of specific IGF-I receptors not involved in stimulation of glucose transport.
abstract: We demonstrate the presence of specific insulinlike growth factor I (IGF-I) receptors in human adipocytes. Competition studies with 125I-labeled IGF-I and unlabeled IGF-I, IGF-II, and insulin showed the specificity of 125I-IGF-I binding to the IGF-I receptors in adipocytes, membranes, and partially purified detergent-solubilized extracts. The monoclonal antibody to the IGF-I receptor (alpha-IR3) inhibits 125I-IGF-I binding and immunoprecipitates the IGF-I receptor. In addition, the alpha-subunit of IGF-I receptor is approximately 10,000 Mr larger than the alpha-subunit of insulin receptor, and IGF-I stimulates phosphorylation of the beta-subunit of the IGF-I receptor. IGF-I stimulates basal glucose transport in human adipocytes, but the concentrations of IGF-I required for half-maximal and maximal stimulation of glucose transport are 800- and 1000-fold greater than that of insulin. The possibility of IGF-I stimulating glucose transport by interacting predominantly with insulin receptors is suggested by data showing that 1) IGF-I competes with insulin-binding sites, 2) there is a lack of an additive effect with IGF-I and insulin in stimulating glucose transport, 3) alpha-IR3, which specifically inhibits IGF-I binding, does not inhibit IGF-I or insulin-stimulated glucose transport, 4) insulin-receptor antibody MA-10 inhibits IGF-I and insulin-stimulated glucose transport, and 5) IGF-I stimulates insulin-receptor autophosphorylation, although its effect is markedly decreased compared with insulin. In summary, human adipocytes possess specific IGF-I receptors. However, IGF-I stimulates glucose transport predominantly by interacting with the insulin receptor.
authors.affiliation: Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354.
authors.forename: M K
authors.initials: MK
authors.lastname: Sinha
authors.forename: C
authors.initials: C
authors.lastname: Buchanan
authors.forename: N
authors.initials: N
authors.lastname: Leggett
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.forename: P G
authors.initials: PG
authors.lastname: Khazanie
authors.forename: R
authors.initials: R
authors.lastname: Dimarchi
authors.forename: W J
authors.initials: WJ
authors.lastname: Pories
authors.forename: J F
authors.initials: JF
authors.lastname: Caro
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008970:Molecular Weight; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000302:isolation & purification / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013002:Somatomedins / Q000494:pharmacology*
chemical_list: D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D011994:Recombinant Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D005947:Glucose