Nature 444, 840-846 (14 December 2006) | doi:10.1038/nature05482; Published online 13 December 2006

Mechanisms linking obesity to insulin resistance and type 2 diabetes

Steven E. Kahn1, Rebecca L. Hull1 and Kristina M. Utzschneider1


Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes. In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance. When insulin resistance is accompanied by dysfunction of pancreatic islet beta-cells — the cells that release insulin — failure to control blood glucose levels results. Abnormalities in beta-cell function are therefore critical in defining the risk and development of type 2 diabetes. This knowledge is fostering exploration of the molecular and genetic basis of the disease and new approaches to its treatment and prevention.

  1. Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, 1660 South Columbian Way, Seattle, Washington 98108, USA.

Correspondence to: S.E.K. (Email:
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