Obesity, Stress, and Diabetes

Science's STKE  19 Oct 2004:
Vol. 2004, Issue 255, pp. tw372
DOI: 10.1126/stke.2552004tw372

Obesity is a major risk factor for type 2 diabetes, but how the two conditions are linked is not fully understood. Özcan et al. (see the Perspective by Muoio and Newgard) identify endoplasmic reticulum (ER) stress as a possible connection. The ER is a network of intracellular membranes involved in membrane and secretory protein synthesis and processing, and its function is sensitive to pathological stress, such as changes in nutrient levels. Obesity triggers ER stress in liver and fat cells, and this stress in turn disrupts insulin signaling. When placed on a high-fat diet, genetically manipulated mice with elevated levels of ER stress developed peripheral insulin resistance at a higher rate than controls. The ER stress signaling pathway may be a useful target for the development of new therapeutics for type 2 diabetes.

U. Özcan, Q. Cao, E. Yilmaz, A.-H. Lee, N. N. Iwakoshi, E. Özdelen, G. Tuncman, C. Görgün, L. H. Glimcher, G. S. Hotamisligil, Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 306, 457-461 (2004). [Abstract] [Full Text]

D. M. Muoio, C. B. Newgard, Insulin resistance takes a trip through the ER. Science 306, 425-426 (2004). [Summary] [Full Text]