Research ArticleAtherosclerosis

Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition

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Science Translational Medicine  29 Apr 2020:
Vol. 12, Issue 541, eaav8824
DOI: 10.1126/scitranslmed.aav8824

From stress to sensitivity

Poor glycemic control drives cardiovascular disease, but aggressive blood glucose lowering does not improve cardiovascular risk. To understand the underlying mechanisms, Akoumianakis et al. studied the relationship between the local redox state of blood vessels and cardiovascular outcomes of patients with coronary atherosclerosis. They found that diseased vessels were insulin resistant and had increased oxidative stress and reduced nitric oxide bioavailability, which could be reversed by treatment with an inhibitor of dipeptidyl peptidase 4 (DPP4). Vascular insulin sensitivity was also restored in mice with atherosclerosis upon treatment with an oral DPP4 inhibitor. Results uncover how DPP4 inhibition induces insulin sensitization in the vascular wall and suggest that cotreatment with insulin may be therapeutic for patients with cardiometabolic disease.

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