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Mechanisms linking obesity to insulin resistance and type 2 diabetes

Nature volume 444, pages 840–846 (2006)Cite this article

Abstract

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 β-cells — the cells that release insulin — failure to control blood glucose levels results. Abnormalities in β-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.

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Figure 1: Relationship between insulin sensitivity and insulin release in health and disease.
Figure 2: Simplified model outlining potential cellular mechanisms of β-cell adaptation to insulin resistance.
Figure 3: Interaction of genes and the environment in individuals who maintain normal glucose tolerance and those who develop type 2 diabetes.
Figure 4: Model of the critical role of impaired insulin release in linking obesity with insulin resistance and type 2 diabetes.

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Acknowledgements

This work was supported in part by the US Department of Veterans Affairs and the NIH. S.E.K. is the recipient of an American Diabetes Association Distinguished Clinical Scientist Award.

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

    Steven E. Kahn, Rebecca L. Hull & Kristina M. Utzschneider

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Kahn, S., Hull, R. & Utzschneider, K. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840–846 (2006). https://doi.org/10.1038/nature05482

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