PMID- 33008044 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201103 IS - 2218-1989 (Print) IS - 2218-1989 (Electronic) IS - 2218-1989 (Linking) VI - 10 IP - 10 DP - 2020 Sep 30 TI - Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect. LID - 10.3390/metabo10100391 [doi] LID - 391 AB - 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), naive 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. FAU - Giglio, Rosaria Vincenza AU - Giglio RV AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Nikolic, Dragana AU - Nikolic D AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Volti, Giovanni Li AU - Volti GL AUID- ORCID: 0000-0002-8678-2183 AD - Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy. FAU - Stoian, Anca Pantea AU - Stoian AP AUID- ORCID: 0000-0003-0555-526X AD - Department of Diabetes, Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania. FAU - Banerjee, Yajnavalka AU - Banerjee Y AUID- ORCID: 0000-0002-7546-8893 AD - College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE. FAU - Magan-Fernandez, Antonio AU - Magan-Fernandez A AUID- ORCID: 0000-0001-6430-2276 AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Castellino, Giuseppa AU - Castellino G AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Patti, Angelo Maria AU - Patti AM AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Chianetta, Roberta AU - Chianetta R AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Castracani, Carlo Castruccio AU - Castracani CC AUID- ORCID: 0000-0002-1002-8969 AD - Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy. FAU - Montalto, Giuseppe AU - Montalto G AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. FAU - Rizvi, Ali A AU - Rizvi AA AD - Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC 29203, USA. AD - Division of Endocrinology, Metabolism, and Lipids Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Sesti, Giorgio AU - Sesti G AD - Department of Clinical and Molecular Medicine, University of Rome La Sapienza, 00182 Rome, Italy. FAU - Rizzo, Manfredi AU - Rizzo M AUID- ORCID: 0000-0002-9549-8504 AD - Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy. AD - Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine, Columbia, SC 29203, USA. LA - eng PT - Journal Article DEP - 20200930 PL - Switzerland TA - Metabolites JT - Metabolites JID - 101578790 PMC - PMC7599907 OTO - NOTNLM OT - cardiometabolic risk OT - epigenetic OT - liraglutide OT - microRNAs OT - type-2 diabetes COIS- The authors have given talks, attended conferences and participated in advisory boards and clinical trials sponsored by various pharmaceutical companies. Prof. Anca Pantea Stoian is currently the Vice President of the Romanian National Diabetes Committee. Prof. Manfredi Rizzo is currently Chief Medical and Scientific Advisor, Diabetes, Novo Nordisk South East Europe, Middle East and Africa (SEEMEA). The authors declare no conflict of interest, financial or otherwise. EDAT- 2020/10/04 06:00 MHDA- 2020/10/04 06:01 PMCR- 2020/10/01 CRDT- 2020/10/03 01:01 PHST- 2020/08/20 00:00 [received] PHST- 2020/09/27 00:00 [revised] PHST- 2020/09/28 00:00 [accepted] PHST- 2020/10/03 01:01 [entrez] PHST- 2020/10/04 06:00 [pubmed] PHST- 2020/10/04 06:01 [medline] PHST- 2020/10/01 00:00 [pmc-release] AID - metabo10100391 [pii] AID - metabolites-10-00391 [pii] AID - 10.3390/metabo10100391 [doi] PST - epublish SO - Metabolites. 2020 Sep 30;10(10):391. doi: 10.3390/metabo10100391.