Glucose Tranporter-4 expression in monocytes: A systematic review Yorgi Mavros a, *, David Simar b , Maria A. Fiatarone Singh a,c,d a Exercise, Health and Performance Faculty Research Group, Faculty of Health Sciences, University of Sydney, East Street, Lidcombe, Sydney, NSW 2141, Australia b School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia c Faculty of Medicine, University of Syndey, Sydney, NSW, Australia d Hebrew SeniorLife and Jean Mayer USDA Human Nutrition Center on Aging, Tufts University, Boston, MA, USA 1. Introduction 1.1. Glucose transporters Of particular interest to the study of the pathophysiology of insulin resistance and type 2 diabetes is the Glucose Tranporter-4 (GLUT-4), which is an isoform of the GLUT family found primarily in insulin sensitive tissues [1]. In fasting and non-exercise (resting) conditions, GLUT-4 is located in small intracellular tubulo-vesicular organelles within skeletal muscle and other insulin sensitive cells. In response to insulin stimulation, it translocates to the plasma membrane of the cell [2–5]. Studies of the kinetics of GLUT-4 translocation have shown that it has a high affinity for glucose, with a K m between 2 and 5 mM [6]. As a result, GLUT-4 is constantly operating at close to its V max over physiological ranges for blood glucose, and so the rate of glucose transport into cells is not determined by glucose concentrations per se, but rather by the response of GLUT-4 to insulin signalling pathways. Secondly, stimulation by insulin increases the V max diabetes research and clinical practice 84 (2009) 123–131 article info Article history: Received 17 June 2008 Received in revised form 10 December 2008 Accepted 9 February 2009 Published on line 14 March 2009 Keywords: Monocyte GLUT-4 Diabetes Insulin resistance Flow cytometry abstract Objective: The purpose of this review was to systematically assess the extent of current knowledge of Glucose Tranporter-4 (GLUT-4) expression in monocytes in humans to address its potential use as a non-invasive and reliable model to investigate the relationships between insulin signalling, GLUT-4 expression and insulin action in vivo. Method: Electronic database searches were performed with the keywords ‘monocyte’, ‘leukocyte’ and ‘white blood cells’, and the terms ‘GLUT’, ‘glucose transporter’ and ‘SLC2A4’ (solute carrier family 2 member 4). Studies were examined for robustness of design and outcomes by consensus of three reviewers. Results: Six cross-sectional or observational studies met the criteria for review. Insulin- stimulated GLUT-4 expression in monocytes from subjects likely to have impaired insulin sensitivity appeared blunted relative to healthy subjects. Conclusion: The available results provide evidence that monocyte GLUT-4 translocation does occur in response to acute insulin exposure, and may be sensitive to the relative state of insulin resistance of the individual. However, due to the limited quantity and robustness of published data, the ultimate utility of monocyte GLUT-4 expression as an index of whole body insulin responsiveness and the clinical relevance of this methodology is unresolved at this time. Crown Copyright # 2009 Published by Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +61 2 9351 9279; fax: +61 2 9351 9204. E-mail address: ymav5521@mail.usyd.edu.au (Y. Mavros). Contents lists available at ScienceDirect Diabetes Research and Clinical Practice journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter . Crown Copyright # 2009 Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2009.02.014