title: The RGD sequence present in IGFBP-2 is required for reduced glucose clearance after oral glucose administration in female transgenic mice.
abstract: Recent studies suggest that insulin-like growth factor-binding protein-2 (IGFBP-2) affects both growth and metabolism. Whereas negative growth effects are primarily due to negative interference with IGF-I, the mechanisms for metabolic interference of IGFBP-2 are less clear. As we demonstrate, overexpression of IGFBP-2 in transgenic mice is correlated with a decelerated clearance of blood glucose after oral administration. IGFBP-2 carries an integrin-binding domain (RGD motif), which has been shown to also mediate IGF-independent effects. We thus asked if higher serum levels of IGFBP-2 without an intact RGD motif would also partially block blood glucose clearance after oral glucose application. In fact, transgenic mice overexpressing mutated IGFBP-2 with higher levels of IGFBP-2 carrying an RGE motif instead of an RGD were not characterized by decelerated glucose clearance. Impaired glucose tolerance was correlated with lower levels of GLUT4 present in plasma membranes isolated from muscle tissues after glucose challenge. At the same time, activation of TBC1D1 was depressed in mice overexpressing wild-type but not mutated IGFBP-2. Although we do not have reason to assume altered activation of IGF-I receptor or PDK1/Akt activation in both models, we have identified increased levels of integrin-linked kinase and focal adhesion kinase dependent on the presence of the RGD motif. From our results we conclude that impaired glucose clearance in female IGFBP-2 transgenic mice is dependent on the presence of the RGD motif and that translocation of GLUT4 in the muscle may be regulated by IGFBP-2 via RGD-dependent mechanisms.
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany;
authors.forename: Anja
authors.initials: A
authors.lastname: Reyer
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany;
authors.forename: Nancy
authors.initials: N
authors.lastname: Schindler
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany;
authors.forename: Daniela
authors.initials: D
authors.lastname: Ohde
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany;
authors.forename: Christina
authors.initials: C
authors.lastname: Walz
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Kunze
authors.affiliation: Institute for Genetics and Biometry, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany; and.
authors.forename: Armin
authors.initials: A
authors.lastname: Tuchscherer
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany; Ligandis GbR, Gülzow-Prüzen, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Wirthgen
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany;
authors.forename: Julia
authors.initials: J
authors.lastname: Brenmoehl
authors.affiliation: Institute for Genome Biology, Leibniz Institute for Farm Animal Biology, Dummerstorf, Germany; hoeflich@fbn-dummerstorf.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hoeflich
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism / Q000235:genetics; D005260:Female; D005947:Glucose / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009842:Oligopeptides / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D018971:Insulin-Like Growth Factor Binding Protein 2; D009842:Oligopeptides; C495693:Slc2a4 protein, mouse; C047981:arginyl-glycyl-aspartic acid; D005947:Glucose