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The endothelial cell: An “early responder” in the development of insulin resistance

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Abstract

Vascular endothelium is an important insulin target and plays a pivotal role in the development of metabolic insulin resistance provoked by the Western lifestyle. It acts as a “first-responder” to environmental stimuli such as nutrients, cytokines, chemokines and physical activity and regulates insulin delivery to muscle and adipose tissue and thereby affecting insulin-mediated glucose disposal by these tissues. In addition, it also regulates the delivery of insulin and other appetite regulating signals from peripheral tissues to the central nervous system thus influencing the activity of nuclei that regulate hepatic glucose production, adipose tissue lipolysis and lipogenesis, as well as food consumption. Resistance to insulin’s vascular actions therefore broadly impacts tissue function and contribute to metabolic dysregulation. Moreover, vascular insulin resistance negatively impacts vascular health by affecting blood pressure regulation, vessel wall inflammation and atherogenesis thereby contributing to the burden of vascular disease seen with diabetes and metabolic syndrome. In the current review, we examined the evidence that supports the general concept of vascular endothelium as a target of insulin action and discussed the biochemical and physiological consequences of vascular insulin resistance.

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Acknowledgments

This work was supported by NIH grants R01DK057878 and R01DK073759 (to E.J.B) and R01HL094722 (to Z.L.), and American Diabetes Association grants 1-11-BS-06 (to E.J.B) and 1-11-CR-30 and 9-09-NOVO-11 (to Z.L.).

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  1. Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA

    Eugene J. Barrett & Zhenqi Liu

  2. University of Virginia Health System, 450 Ray C. Hunt Drive, P.O. Box 801410, Charlottesville, VA, 22908, USA

    Eugene J. Barrett

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Correspondence to Eugene J. Barrett.

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Barrett, E.J., Liu, Z. The endothelial cell: An “early responder” in the development of insulin resistance. Rev Endocr Metab Disord 14, 21–27 (2013). https://doi.org/10.1007/s11154-012-9232-6

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