Binding between IGF‐1 and IGFBP‐3 is not influenced by glucose or 2‐DG

Abstract

A recent report details that 2‐deoxy‐D‐glucose (2‐DG), a well known inhibitor of glycolysis and a candidate antineoplastic agent, also induces insulin‐like growth factor 1 receptor (IGF‐1R) signaling through the inhibition of insulin‐like growth factor 1/ insulin‐like growth factor binding protein 3 (IGF‐1/IGFBP‐3) complex formation. The authors hypothesized that disrupted IGF‐1/IGFBP‐3 binding by 2‐DG led to increased free IGF‐1 concentrations and, consequently, activation of IGF‐1R downstream pathways. Since their report suggests unprecedented off‐target effects of 2‐DG, this has profound implications for the fields of metabolism and oncology. Using ELISA, surface plasmon resonance (SPR), and novel “intensity‐fading” mass spectrometry (MS), we now provide a detailed characterization of complex formation between IGF‐1 and IGFBP‐3. All three of these independent methods demonstrated that there was no effect of glucose or 2‐DG on the interaction between IGF‐1 and IGFBP‐3. While the mechanism implicated in 2‐DG induced increase in IGF‐1R signaling remains unresolved, our observations clearly do not support the hypothesis that 2‐DG inhibits IGF‐1/IGFBP‐3 complex formation.