TY - JOUR
T1 - Metformin-mediated epigenetic modifications in diabetes and associated conditions
T2 - Biological and clinical relevance
AU - Giordo, Roberta
AU - Posadino, Anna Maria
AU - Mangoni, Arduino Aleksander
AU - Pintus, Gianfranco
PY - 2023/9
Y1 - 2023/9
N2 - 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.
AB - 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.
KW - Diabetes
KW - DNA methylation
KW - Epigenetics
KW - Epigenome
KW - Histone modifications
KW - Metformin
KW - ncRNAs
UR - http://www.scopus.com/inward/record.url?scp=85166960210&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2023.115732
DO - 10.1016/j.bcp.2023.115732
M3 - Review article
C2 - 37541452
AN - SCOPUS:85166960210
SN - 0006-2952
VL - 215
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
M1 - 115732
ER -