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

被引:29
作者
Luna-Marco, Clara [1 ]
de Maranon, Arantxa M. [1 ,2 ]
Hermo-Argibay, Alberto [1 ]
Rodriguez-Hernandez, Yohaly [1 ]
Hermenejildo, Jonathan [1 ]
Fernandez-Reyes, Meylin [1 ]
Apostolova, Nadezda [3 ,4 ]
Vila, Jose [5 ]
Sola, Eva [1 ]
Morillas, Carlos [1 ]
Rovira-Llopis, Susana [1 ,5 ]
Rocha, Milagros [1 ]
Victor, Victor M. [1 ,4 ,5 ]
机构
[1] Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABIO, Serv Endocrinol & Nutr, Valencia, Spain
[2] Univ Coll Cork, Coll Med & Hlth, Canc Res UCC, Cork, Ireland
[3] Univ Valencia, Dept Pharmacol, Valencia, Spain
[4] Natl Network Biomed Res Hepat & Digest Dis CIBEReh, Valencia, Spain
[5] Univ Valencia, INCLIVA Biomed Res Inst Valencia, Dept Physiol, Valencia, Spain
来源
REDOX BIOLOGY | 2023年 / 66卷
关键词
Type; 2; diabetes; GLP-1; RA; Mitochondrial dysfunction; Leukocytes; Oxidative stress; Atherogenesis/atherosclerosis; GLUCAGON-LIKE PEPTIDE-1; LEUKOCYTE/ENDOTHELIAL CELL-INTERACTIONS; INSULIN-RESISTANCE; ATHEROSCLEROSIS; LIRAGLUTIDE; ASSOCIATION; ADHESION; RISK;
D O I
10.1016/j.redox.2023.102849
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Objective: 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, leukocyteendothelial interactions, inflammation and carotid intima-media thickness (CIMT) in T2D patients. Research design and methods: 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. Results: 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, TNF & alpha; 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. Conclusions: GLP-1 RA treatment improves the redox state and mitochondrial respiration, and reduces leukocyteendothelial interactions, inflammation and CIMT in T2D patients, thereby potentially diminishing the risk of atherosclerosis and CVDs.
引用
收藏
页数:7
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