4.6 Review

Diabetes pathogenesis and management: the endothelium comes of age

Journal

JOURNAL OF MOLECULAR CELL BIOLOGY
Volume 13, Issue 7, Pages 500-512

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjab024

Keywords

diabetes; insulin resistance; endothelium; vascular function

Categories

Funding

  1. National Institutes of Health [R01DK125330, R01DK102359, F32DK121431]
  2. National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR003015, KL2TR003016]
  3. VA Merit Review [BX002046]
  4. VA Clinical Merit Review [CX001532, UL1 TR000154, P30 DK116073]

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Endothelial cells play a crucial role in the development of insulin resistance and type 2 diabetes, with their dysfunction contributing to various metabolic complications. Various therapeutic modalities can improve endothelial function, reducing the onset and complications of diabetes.
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.

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