Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect
Rosaria Vincenza Giglio,
Dragana Nikolic,
Giovanni Li Volti,
Anca Pantea Stoian,
Yajnavalka Banerjee,
Antonio Magan-Fernandez,
Giuseppa Castellino,
Angelo Maria Patti,
Roberta Chianetta,
Carlo Castruccio Castracani,
Giuseppe Montalto,
Ali A. Rizvi,
Giorgio Sesti,
Manfredi Rizzo
Affiliations
Rosaria Vincenza Giglio
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Dragana Nikolic
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Giovanni Li Volti
Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy
Anca Pantea Stoian
Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
Yajnavalka Banerjee
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE
Antonio Magan-Fernandez
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Giuseppa Castellino
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Angelo Maria Patti
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Roberta Chianetta
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Carlo Castruccio Castracani
Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy
Giuseppe Montalto
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Ali A. Rizvi
Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC 29203, USA
Giorgio Sesti
Department of Clinical and Molecular Medicine, University of Rome La Sapienza, 00182 Rome, Italy
Manfredi Rizzo
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, p = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, p = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, p = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, p = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, p = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) (p = 0.0401), 1.91 (3.64) (p = 0.0401) and 2.09 (11.0) (p = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide’s benefits and may represent useful targets for cardiometabolic management.
