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.
Epidermal Growth Factor Induces Glucose Storage in Transgenic 3T3-L1 Adipocytes Overexpressing Epidermal Growth Factor Receptors
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Mark Van Epps-Fung, Robert W Hardy, Jodie Williford, Kiran Gupta, Alan Wells; Epidermal Growth Factor Induces Glucose Storage in Transgenic 3T3-L1 Adipocytes Overexpressing Epidermal Growth Factor Receptors. Diabetes 1 November 1996; 45 (11): 1619–1625. https://doi.org/10.2337/diab.45.11.1619
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