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
Keywords: 
Materias Investigacion::Ciencias de la Salud::Especialidades médicas
GLP-1
Oxidative stress
Cardiac remodeling
Cardiovascular events
Type 2 diabetes mellitus
Issue Date: 
2015
Publisher: 
Elsevier
ISSN: 
0891-5849
Citation: 
Ravassa, S. (Susana); Beaumont, J. (Javier); Huerta, A. (Ana); et al. "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". Free Radical Biology and Medicine. 81, 2015, 1 - 12
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 exhibit CR and be at higher risk for CVE. In addition, GLP-1 exerts antioxidant effects in HL-1 palmitate-overloaded cardiomyocytes. It is proposed that therapies aimed to increase GLP-1 may counteract OS, protect from CR, and prevent CVE in patients with T2DM.

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