Obesity and Insulin Resistance: An Ongoing Saga

Abstract

Although the adverse effects of excess adiposity on insulin-mediated glucose uptake (IMGU) are well-recognized (1,2), the mechanism and/or mechanisms that explain this relationship continue to be debated. The article by Kursawe et al. (3) in this issue of Diabetes provides another, and potentially important, mechanism linking excess adiposity and IMGU. However, to put their findings into perspective, it might be helpful to provide a brief history of other approaches to this issue. The experimental methods utilized in earlier mechanistic studies are reminiscent of the study by Kursawe et al. (3) and led to the view that metabolic abnormalities associated with obesity were related to changes in fat cell size rather than number (4–7). For example, ex vivo studies on adipose tissue isolated from obese humans demonstrated that the larger the fat cell, the more diminished the response to insulin (4). Furthermore, insulin sensitivity of isolated fat improved following weight loss-associated decreases in fat cell size. Although these data indicated that differences in fat cell size affected insulin action, the fat cell is not a major consumer of glucose (8). Thus, these data do not necessarily explain why large fat cells would have an adverse effect on whole-body IMGU. Furthermore, why some individuals had large fat cells and …