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Maria M. Docanto. 1 Metabolism & Cancer Laboratory, Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Victoria, Australia.
Seungmin Ham. 1 Metabolism & Cancer Laboratory, Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Victoria, Australia.
Anne Corbould. 1 Metabolism & Cancer Laboratory, Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Victoria, Australia. 2 Department of Physiology, Monash University, Clayton, Victoria, Australia.
Kristy A. Brown. 1 Metabolism & Cancer Laboratory, Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Victoria, Australia. 2 Department of Physiology, Monash University, Clayton, Victoria, Australia. 3 Department of Molecular and Translational Sciences, Monash University, Clayton, Victoria, Australia.
Address correspondence to: Dr. Kristy A. Brown, Metabolism & Cancer Laboratory, MIMR-PHI Institute of Medical Research, 27-31 Wright Street, Clayton, Victoria 3168, Australia, E-mail: [email protected]
Introduction
Obesity affects approximately one-third of the population and is recognized to be associated with a state of low-grade chronic inflammation. This occurs as a consequence of the recruitment of macrophages to necrotic adipocytes and reports have suggested that these inflammatory cells make up ∼40% of the total cells found in obese adipose tissue (Weisberg and others 2003). Inflammatory cytokines and prostaglandins (PGs) produced in obesity include interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNFα), and PGE2 . These inflammatory mediators have been shown to inhibit adipocyte differentiation as well as impact the function of mature adipocytes. Adipose tissue inflammation is associated with an impaired response to insulin, and hence, a decrease in insulin-mediated glucose uptake.
Adipose tissue insulin resistance is believed to be a key contributor to whole body insulin resistance and the development of type II diabetes. Preadipocytes or adipose stromal cells are adipocyte precursors and have been shown to express relatively low levels of the insulin receptor compared to mature adipocytes (Back and Arnqvist 2009). These cells also tend to have undetectable levels of the insulin-dependent glucose transporter GLUT4 (Hauner and others 1998). Nevertheless, adipose stromal cells have a higher rate of basal glucose uptake than their differentiated counterparts and their numbers are increased in obesity (van Harmelen and others 2003).
The basal uptake of glucose is dependent on insulin-independent glucose transporters. Of the 13 members of the facilitative sugar transporters, GLUT1 and GLUT3 Class I facilitative transporters have been shown to...