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Diabetes pathogenesis and management: the endothelium comes of age
Kaitlin M. Love1 , Eugene J. Barrett11 , Steven K. Malin2,3,4,5 , Jane E.B. Reusch6,7,8 , Judith G. Regensteiner6,7 , Zhenqi Liu1,*
1Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
2Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ, USA
3Division of Endocrinology, Metabolism and Nutrition, Rutgers University, New Brunswick, NJ, USA
4New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA
5Institute of Translational Medicine and Research, Rutgers University, New Brunswick, NJ, USA
6Center for Women’s Health Research, University of Colorado School of Medicine, Aurora, CO, USA
7Department of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA
8Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, USA
*Correspondence to:Zhenqi Liu , Email:zl3e@virginia.edu
J Mol Cell Biol, Volume 13, Issue 7, July 2021, Pages 500-512  https://doi.org/10.1093/jmcb/mjab024
Keyword: diabetes, insulin resistance, endothelium, vascular function

Endothelium, acting as a barrier, protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered function. Endothelial insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease, can co-exist with and even contribute to the development of metabolic insulin resistance, and promote vascular complications in those affected. The impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location, resulting in decreased arterial plasticity, increased atherosclerosis and vascular resistance, and decreased tissue perfusion. Women with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease, likely related to differential sex-hormone endothelium effects. Thus, reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications, in the resistance arteries lead to better blood pressure control, and in the microvasculature lead to less microvascular complications and more effective tissue perfusion. Multiple diabetes therapeutic modalities, including medications and exercise training, improve endothelial insulin action and vascular function. This action may delay the onset of type 2 diabetes and/or its complications, making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.