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Mechanisms linking obesity to insulin resistance and type 2 diabetes

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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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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