Cited by 145Nitric Oxide and Endothelin EffectsDiabetes, Cardiovascular Risks, and LipoproteinsCardiovascular Function and Risk Factors

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The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update

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Zhang, Hanrui, Dellsperger, Kevin C., Zhang, Cuihua·2012·Basic Research in Cardiology

DOI 10.1007/s00395-011-0237-1PMC PMC5512574

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Abstract

Despite abundant clinical evidence linking metabolic abnormalities to diabetic vasculopathy, the molecular basis of individual susceptibility to diabetic vascular complications is still largely undetermined. Endothelial dysfunction in diabetes-associated vascular complications is considered an early stage of vasculopathy and has attracted considerable research interests. Type 2 diabetes is characterized by metabolic abnormalities, such as hyperglycemia, excess liberation of free fatty acids (FFA), insulin resistance and hyperinsulinemia. These abnormalities exert pathological impact on endothelial function by attenuating endothelium-mediated vasomotor function, enhancing endothelial apoptosis, stimulating endothelium activation/endothelium-monocyte adhesion, promoting an atherogenic response and suppressing barrier function. There are multiple signaling pathways contributing to the adverse effects of glucotoxicity on endothelial function. Insulin maintains the normal balance for release of several factors with vasoactive properties. Abnormal insulin signaling in the endothelium does not affect the whole-body glucose metabolism, but impairs endothelial response to insulin and accelerates atherosclerosis. Excessive level of FFA is implicated in the pathogenesis of insulin resistance. FFA induces endothelial oxidative stress, apoptosis and inflammatory response, and inhibits insulin signaling. Although hyperglycemia, insulin resistance, hyperinsulinemia and dyslipidemia independently contribute to endothelial dysfunction via various distinct mechanisms, the mutual interactions may synergistically accelerate their adverse effects. Oxidative stress and inflammation are predicted to be among the first alterations which may trigger other downstream mediators in diabetes associated with endothelial dysfunction. These mechanisms may provide insights into potential therapeutic targets that can delay or reverse diabetic vasculopathy.

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Authors: Zhang, H., Dellsperger, K. C., & Zhang, C.
Affiliations: University of Missouri (US)
Corresponding author: Zhang, Hanrui
ORCID: Zhang, Hanrui
Dellsperger, Kevin C.
Zhang, Cuihua
Venue: Basic Research in Cardiology
Publisher: Springer Science and Business Media LLC
Published: 2011-12-22
Volume: 107
Issue: 1
Pages: 237-237
ISSN: 0003-9217 (ISSN-L)
0300-8428
1435-1803
DOI: 10.1007/s00395-011-0237-1
PMC: PMC5512574
OpenAlex: W2019514289
Cited by: 144
References: 109
Citations by year: 2026: 10 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 11 · 2021: 7 · 2020: 6 · 2019: 5 · 2018: 11 · 2017: 7 · 2016: 15 · 2015: 11 · 2014: 10 · 2013: 16 · 2012: 12
FWCI: 1.30
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Basic Research in Cardiology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association
National Institutes of Health
National Heart, Lung, and Blood Institute (R01HL085119, R01HL077566)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
Keywords: endothelial dysfunction, type 2 diabetes, diabetic vascular disease, hyperglycemia, free fatty acids, insulin resistance, hyperinsulinemia, dyslipidemia, glucotoxicity, endothelial oxidative stress, endothelial cell apoptosis, endothelial inflammation, endothelial barrier function, atherosclerosis, insulin signaling, therapeutic target
MeSH terms: Animals, Diabetes Mellitus, Type 2, Endothelium, Vascular, Fatty Acids, Nonesterified, Humans, Hyperglycemia, Insulin Resistance, Vasomotor System

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The link between metabolic abnormalities and endothelial dysfunction in type 2 diabetes: an update

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