Access

Letter

Nature 440, 944-948 (13 April 2006) | doi:10.1038/nature04634; Received 23 November 2005; Accepted 6 February 2006

Reactive oxygen species have a causal role in multiple forms of insulin resistance

Nicholas Houstis1,2,3, Evan D. Rosen1,4 & Eric S. Lander1,2,3,5

  1. Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02141, USA
  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
  3. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA
  4. Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02214, USA
  5. Department of Systems Biology, Harvard Medical School, Boston, Massachusetts 02115, USA

Correspondence to: Evan D. Rosen1,4Eric S. Lander1,2,3,5 Correspondence and requests for materials should be addressed to E.D.R. (Email: erosen@bidmc.harvard.edu) or E.S.L. (Email: lander@broad.mit.edu).

Top

Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested1, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

RESEARCH

Weight Gain Induced by High-Fat Feeding Involves Increased Liver Oxidative Stress *

Obesity Scientific Correspondence

The hormone resistin links obesity to diabetes

Nature Article (18 Jan 2001)