Epidermal growth factor induces glucose storage in transgenic 3T3-L1 adipocytes overexpressing epidermal growth factor receptors.

Academic Article

Abstract

  • 3T3-L1 adipocytes represent an established physiological model for studying glucose uptake and storage. Overexpression of epidermal growth factor (EGF) receptors in these cells (200,000-250,000 receptors per cell) confers EGF-inducible GLUT4-mediated glucose uptake (17). We now report that EGF receptor (EGFR)-mediated signals can induce incorporation of glucose into glycogen and lipids in these cells. Incorporation into lipids was stimulated to similar levels by insulin or EGF in adipocytes expressing full-length (wild type) EGFR (2.05 +/- 0.26-fold for insulin vs. 2.28 +/- 0.15-fold for EGF). EGF induced incorporation into glycogen at roughly 60% of the level of insulin (4.53 +/- 0.57-fold for insulin vs. 2.76 +/- 0.25-fold for EGF); this corresponded with similarly lower levels of glycogen synthase activation by EGF relative to insulin stimulation. EGFR kinase activity was required for induced storage because a kinase-inactive (M721) EGFR failed to stimulate glucose incorporation into glycogen or lipids. EGFRs that lack all or part of the unique EGFR COOH-terminal tail induced glucose incorporation at levels similar to that stimulated by full-length (wild type) EGFR. Thus, domains in the COOH-terminal tail of the EGFR, which are necessary for stimulating glucose transport, are not required for signaling EGF-induced glucose storage. EGF-induced glucose storage did not require de novo protein synthesis, suggesting that EGFR signaling uses existing pathways in the adipocytes. These data demonstrate that signaling pathways for EGFR-mediated glucose storage and GLUT4-mediated glucose transport diverge at the receptor level. Thus, EGF-induced glucose storage can be achieved in the absence of induced GLUT4-mediated glucose transport.
  • Authors

    Published In

  • Diabetes  Journal
  • Keywords

  • 3T3 Cells, Adipocytes, Animals, Cell Differentiation, Epidermal Growth Factor, ErbB Receptors, Glucose, Glucose Transporter Type 4, Glycogen, Glycogen Synthase, Insulin, Mice, Monosaccharide Transport Proteins, Muscle Proteins, Mutagenesis, Phosphorylation, Recombinant Proteins, Sequence Deletion, Signal Transduction, Transfection
  • Authorlist

  • Van Epps-Fung M; Hardy RW; Williford J; Gupta K; Wells A
  • Start Page

  • 1619
  • End Page

  • 1625
  • Volume

  • 45
  • Issue

  • 11