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

• DOI: 10.1016/j.redox.2023.102849
• Publication Date: 2023-08-14T15:55:09Z
• Authors: Clara Luna-Marco; Arantxa M. de Mar...; Alberto Hermo-Arg...; Yohaly Rodriguez-...; Jonathan Hermenej...; Meylin Fernandez-...; Nadezda Apostolova; Jose Vila; Eva Sola; Carlos Morillas; Susana Rovira-Llopis; Milagros Rocha; Victor M. Victor
• Keywords: Inflammation; Medicine (General); QH301-705.5; Atherogenesis/atherosclerosis; Endothelial Cells; Type 2 diabetes; Atherosclerosis; Carotid Intima-Media Thickness; Glucagon-Like Peptide-1 Receptor; 3. Good health; R5-920; Diabetes Mellitus, Type 2; Oxidative stress; Cardiovascular Diseases; Glucagon-Like Peptide 1; Leukocytes; Humans; Endothelium; Biology (General); GLP-1 RA; Mitochondrial dysfunction; Reactive Oxygen Species; Research Paper

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.