Individuals who are obese have an increased risk of developing type 2 diabetes, in part because they often become resistant to the effects of the hormone insulin. Resistin is a soluble factor produced by fat cells (adipocytes) that is linked to the development of insulin resistance in mice. However, studies have thus far failed to determine such a clear association in humans.
But now, Mitchell Lazar and colleagues, at the University of Pennsylvania, Philadelphia, have determined that human resistin contributes to the development of insulin resistance in mice.
The research appears online, Feb. 2nd, 2009, in the Journal of Clinical Investigation.
One factor that has complicated studies attempting to determine the role of resistin in the development of insulin resistance in humans, is that resistin is produced mainly by immune cells known as macrophages in humans, whereas it is produced by adipocytes in mice.
To overcome this issue, the authors generated mice lacking mouse resistin and expressing human resistin in macrophages. When these mice were fed a high-fat diet, they developed inflammation of the fat tissue, which led to altered levels of fats in the blood and, ultimately, to insulin resistance.
It is hoped that future studies using these mice will help determine the therapeutic potential of modulating levels of human resistin.
- Mohammed Qatanani, Nava R. Szwergold, David R. Greaves, Rexford S. Ahima, Mitchell A. Lazar. Macrophage-derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J. Clin. Invest., 2009; DOI: 10.1172/JCI37273
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