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 con-centrations, 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.

Metformin-mediated epigenetic modifications in diabetes and associated conditions: Biological and clinical relevance / Giordo, Roberta; Posadino, Anna Maria; Mangoni, Arduino Aleksander; Pintus, Gianfranco. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 1873-2968. - 215:(2023). [10.1016/j.bcp.2023.115732]

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

Giordo, Roberta;Posadino, Anna Maria;Mangoni, Arduino Aleksander;Pintus, Gianfranco
2023-01-01

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 con-centrations, 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.
2023
Metformin-mediated epigenetic modifications in diabetes and associated conditions: Biological and clinical relevance / Giordo, Roberta; Posadino, Anna Maria; Mangoni, Arduino Aleksander; Pintus, Gianfranco. - In: BIOCHEMICAL PHARMACOLOGY. - ISSN 1873-2968. - 215:(2023). [10.1016/j.bcp.2023.115732]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/329416
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