SYM-37-02

Phosphoproteomic analysis of insulin resistance

DJ Fazakerley1, R Chaudhuri1, RCJ D'Souza1, BL Parker1, SJ Humphrey1, JR Krycer1, KC Thomas1, M Holliday1 and DE James1,2

  1. School of Life and Environmental Sciences, The Charles Perkins Centre, University of Sydney, NSW 2006, Australia
  2. School of Medicine, The Charles Perkins Centre, University of Sydney, NSW 2006, Australia

Insulin resistance is a major risk factor for the development of a number of metabolic diseases including type 2 diabetes. Insulin signalling regulates a range of cellular processes via protein phosphorylation, yet there is strong evidence that insulin resistance is selective for glucose transport and that other processes remain insulin-responsive. This implies that there is not a general defect in insulin signalling and raises the question of how the signalling network is altered to specifically perturb glucose transport. To address this we utilised mass spectrometry-based phosphoproteomics to explore the insulin signalling network in adipose tissue under conditions that cause insulin resistance. Paradoxically, we found that many phosphosites were uniquely insulin responsive under insulin resistant conditions. We are currently investigating how this rewiring drives selective defects in regulated glucose transport.