AUTHOR=Benak Daniel , Benakova Stepanka , Plecita-Hlavata Lydie , Hlavackova Marketa TITLE=The role of m6A and m6Am RNA modifications in the pathogenesis of diabetes mellitus JOURNAL=Frontiers in Endocrinology VOLUME=Volume 14 - 2023 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1223583 DOI=10.3389/fendo.2023.1223583 ISSN=1664-2392 ABSTRACT=The rapidly developing research field of epitranscriptomics has recently emerged into the spotlight of researchers due to its vast regulatory effects on gene expression and thereby cellular physiology and pathophysiology. N 6 -methyladenosine (m 6 A) and N 6 ,2'-O-dimethyladenosine (m 6 Am) are among the most prevalent and well-characterized modified nucleosides in eukaryotic RNA. Both of these modifications are dynamically regulated by a complex set of epitranscriptomic regulators called writers, readers, and erasers. Altered levels of m 6 A and also several regulatory proteins were already associated with diabetic tissues. This review summarizes the current knowledge and gaps about m 6 A and m 6 Am modifications and their respective regulators in the pathophysiology of diabetes mellitus. It focuses mainly on the more prevalent type 2 diabetes mellitus (T2DM) and its treatment by metformin, the first-line antidiabetic agent. A better understanding of epitranscriptomic modifications in this highly prevalent disease deserves further investigation and might reveal clinically relevant discoveries in the future.