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Correspondence: Ali A. Rizvi, arizvi4@emory.edu, Tel. +1-(404)-778-2064

Author contributions: Design of the study: M.R., D.N., G.L.V. and A.A.R.; methodology: M.R., R.V.G., D.N., C.C.C., G.C. and G.L.V.; validation: A.P.S., Y.B., A.A.R. and G.S.; statistical analysis: R.V.G., D.N. and A.M.-F.;

laboratory investigation: R.V.G., D.N., R.C., G.L.V., G.C. and C.C.C.; clinical investigation: M.R., A.M.P. and G.M.; data curation: R.V.G. and D.N.; writing—original draft preparation: M.R., D.N. and A.A.R.; writing—critical review and editing: R.V.G., A.P.S., Y.B. and G.S. All authors have read and agreed to the published version of the manuscript.

We want to thank all the volunteers who participated in this study. A.M.F. participated in this study through an International PhD programme in collaboration with the University of Granada, under the FPU research fellowship program (Ministry of Education and Science, Spain).

The authors wish to thank Francisco Mesa from the University of Granada for valuable scientific support during the study.

Disclosures: 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.

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Research Funding:

This research received no external funding and was performed independently, using University research funds only. The authors did not receive financial or professional help with the preparation of the manuscript.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • liraglutide
  • microRNAs
  • type-2 diabetes
  • cardiometabolic risk
  • epigenetic
  • Intima-media thickness
  • Metabolic syndrome
  • Cardiovascular disease
  • Oxidative stress
  • Peptide-1 GLP-1
  • Expression
  • Targets
  • Management
  • Inflammation

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect

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Journal Title:

Metabolites

Volume:

Volume 10, Number 10

Publisher:

, Pages 1-14

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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