Metformin-mediated epigenetic modifications in diabetes and associated conditions: Biological and clinical relevance

Roberta Giordo, Anna Maria Posadino, Arduino Aleksander Mangoni, Gianfranco Pintus

Research output: Contribution to journalReview articlepeer-review

8 Downloads (Pure)

Abstract

An intricate interplay between genetic and environmental factors contributes to the development of type 2 diabetes (T2D) and its complications. Therefore, it is not surprising that the epigenome also plays a crucial role in the pathogenesis of T2D. Hyperglycemia can indeed trigger epigenetic modifications, thereby regulating different gene expression patterns. Such epigenetic changes can persist after normalizing serum glucose concentrations, suggesting the presence of a ‘metabolic memory’ of previous hyperglycemia which may also be epigenetically regulated. Metformin, a derivative of biguanide known to reduce serum glucose concentrations in patients with T2D, appears to exert additional pleiotropic effects that are mediated by multiple epigenetic modifications. Such modifications have been reported in various organs, tissues, and cellular compartments and appear to account for the effects of metformin on glycemic control as well as local and systemic inflammation, oxidant stress, and fibrosis. This review discusses the emerging evidence regarding the reported metformin-mediated epigenetic modifications, particularly on short and long non-coding RNAs, DNA methylation, and histone proteins post-translational modifications, their biological and clinical significance, potential therapeutic applications, and future research directions.

Original languageEnglish
Article number115732
Number of pages9
JournalBiochemical Pharmacology
Volume215
Early online date2 Aug 2023
DOIs
Publication statusPublished - Sept 2023

Keywords

  • Diabetes
  • DNA methylation
  • Epigenetics
  • Epigenome
  • Histone modifications
  • Metformin
  • ncRNAs

Fingerprint

Dive into the research topics of 'Metformin-mediated epigenetic modifications in diabetes and associated conditions: Biological and clinical relevance'. Together they form a unique fingerprint.

Cite this