Association of low GLP-1 with oxidative stress is related to cardiac disease and outcome in patients with type 2 diabetes mellitus: A pilot study
Abstract
Oxidative stress (OS) contributes to cardiovascular damage in type 2 diabetes mellitus (T2DM). The peptide glucagon-like peptide-1 (GLP-1) inhibits OS and exerts cardiovascular protective actions. Our aim was to investigate whether cardiac remodeling (CR) and cardiovascular events (CVE) are associated with circulating GLP-1 and biomarkers of OS in T2DM patients. We also studied GLP-1 antioxidant effects in a model of cardiomyocyte lipotoxicity. We examined 72 T2DM patients with no coronary or valve heart disease and 14 nondiabetic subjects. A median of 6 years follow-up information was obtained in 60 patients. Circulating GLP-1, dipeptidyl peptidase-4 activity, and biomarkers of OS were quantified. In T2DM patients, circulating GLP-1 decreased and OS biomarkers increased, compared with nondiabetics. Plasma GLP-1 was inversely correlated with serum 3-nitrotyrosine in T2DM patients. Patients showing high circulating 3-nitrotyrosine and low GLP-1 levels exhibited CR and higher risk for CVE, compared to the remaining patients. In palmitate-stimulated HL-1 cardiomyocytes, GLP-1 reduced cytosolic and mitochondrial oxidative stress, increased mitochondrial ATP synthase expression, partially restored mitochondrial membrane permeability and cytochrome c oxidase activity, blunted leakage of creatine to the extracellular medium, and inhibited oxidative damage in total and mitochondrial DNA. These results suggest that T2DM patients with reduced circulating GLP-1 and exacerbated OS may ex…
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Ravassa et al. found higher 3-NT levels in T2D patients with additional cardiovascular events.
“For instance, while Ravassa et al. found higher 3-NT levels in T2D patients with additional cardiovascular events, no differences were observed by Segre and colleagues although baseline parameters of the study populations and the used methods were similar [189,190].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [189]
Segre et al. observed no differences in 3-NT levels in their study.
“For instance, while Ravassa et al. found higher 3-NT levels in T2D patients with additional cardiovascular events, no differences were observed by Segre and colleagues although baseline parameters of the study populations and the used methods were similar [189,190].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [189]
Baseline parameters and methods used in the Ravassa and Segre studies were similar.
“For instance, while Ravassa et al. found higher 3-NT levels in T2D patients with additional cardiovascular events, no differences were observed by Segre and colleagues although baseline parameters of the study populations and the used methods were similar [189,190].”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [189]
In T2D patients, 3-NT levels are elevated compared to non-diabetic subjects (serum, ELISA).
“Elevated levels of 3-NT in T2D patients”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [189]
In T2D patients, 3-NT levels are higher in those with cardiovascular events compared to those without.
“Higher 3-NT levels in T2D patients with cardiovascular events”
From Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases (2021) · cites this paper as [189]
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References 52 · Cited by 34
- Authors
- Ravassa, S., Beaumont, J., Huerta, A., Barba, J., Coma-Canella, I., González, A., López, B., & Díez, J.
- Affiliations
- Centro de Investigación Médica Aplicada (ES)
- Universidad de Navarra (ES)
- Clinica Universidad de Navarra (ES)
- Corresponding author
- Ravassa, Susana
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 81
- Pages
- 1-12
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W1991207338
- Cited by
- 34
- References
- 52
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 4
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion)
- Funders
- Ministry of Economy and Competitiveness (12/0042/0009, PI12/02252)
- European Union (FP7-HEALTH-2011-278249, HEALTH-2012-305507)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- glucagon-like peptide-1, oxidative stress, type 2 diabetes, cardiac remodeling, cardiovascular events, nitrotyrosine, dipeptidyl peptidase IV, palmitate, mitochondrial dysfunction, antioxidant activity, cardiovascular risk
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Aged, Animals, Antioxidants, Cardiovascular System, Cell Line, Deoxyguanosine, Diabetes Mellitus, Type 2, Female, Cardiomegaly, Humans, Male, Middle Aged, Mitochondria, Pilot Projects, Retrospective Studies, Tyrosine, Case-Control Studies, Oxidative Stress, Dipeptidyl Peptidase 4, Palmitic Acid, Ventricular Remodeling, Myocytes, Cardiac, Mice, Glucagon-Like Peptide 1, Atrial Remodeling
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