Effects of GLP-1 receptor agonists on mitochondrial function, inflammatory markers and leukocyte-endothelium interactions in type 2 diabetes

• Published in: Redox biology Vol. 66; p. 102849
• Main Authors: Luna-Marco, Clara, de Marañon, Arantxa M., Hermo-Argibay, Alberto, Rodriguez-Hernandez, Yohaly, Hermenejildo, Jonathan, Fernandez-Reyes, Meylin, Apostolova, Nadezda, Vila, Jose, Sola, Eva, Morillas, Carlos, Rovira-Llopis, Susana, Rocha, Milagros, Victor, Victor M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2023; Elsevier
• Subjects: Atherogenesis/atherosclerosis; GLP-1 RA; Leukocytes; Mitochondrial dysfunction; Oxidative stress; Research Paper; Type 2 diabetes; Type 2 diabetes; GLP-1 RA; Oxidative stress; Atherogenesis/atherosclerosis; Mitochondrial dysfunction; Leukocytes
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2023.102849

Type 2 diabetes (T2D) is linked to metabolic, mitochondrial and inflammatory alterations, atherosclerosis development and cardiovascular diseases (CVDs). The aim was to investigate the potential therapeutic benefits of GLP-1 receptor agonists (GLP-1 RA) on oxidative stress, mitochondrial respiration, leukocyte-endothelial interactions, inflammation and carotid intima–media thickness (CIMT) in T2D patients. Type 2 diabetic patients (255) and control subjects (175) were recruited, paired by age and sex, and separated into two groups: without GLP-1 RA treatment (196) and treated with GLP-1 RA (59). Peripheral blood polymorphonuclear leukocytes (PMNs) were isolated to measure reactive oxygen species (ROS) production by flow cytometry and oxygen consumption with a Clark electrode. PMNs were also used to assess leukocyte-endothelial interactions. Circulating levels of adhesion molecules and inflammatory markers were quantified by Luminex's technology, and CIMT was measured as surrogate marker of atherosclerosis. Treatment with GLP-1 RA reduced ROS production and recovered mitochondrial membrane potential, oxygen consumption and MPO levels. The velocity of leukocytes rolling over endothelial cells increased in PMNs from GLP-1 RA-treated patients, whereas rolling and adhesion were diminished. ICAM-1, VCAM-1, IL-6, TNFα and IL-12 protein levels also decreased in the GLP-1 RA-treated group, while IL-10 increased. CIMT was lower in GLP-1 RA-treated T2D patients than in T2D patients without GLP-1 RA treatment. GLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyte-endothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs. [Display omitted] •Risk of atherosclerosis and cardiovascular diseases is higher in type 2 diabetes.•The question was to investigate GLP-1 RA benefits on diabetes-related factors.•GLP-1 RA improved the redox state and mitochondrial respiration of leukocytes.•GLP-1 RA diminished leukocyte-endothelial interactions, inflammation and CIMT.•The risk of cardiovascular diseases could be reduced with GLP-1 RA treatment.