MiRNAs in hyperglycemia-induced metabolic memory: established mechanisms and emerging nuclear activation concepts

Hyperglycemia-induced metabolic memory refers to the phenomenon in which cells and tissues retain the persistent damage caused by elevated blood glucose even after glucose levels have returned to normal. Studies have demonstrated that noncoding RNAs, particularly microRNAs (miRNAs), contribute to hyperglycemia-induced metabolic memory through the epigenetic regulation of gene expression. Unlike the canonical function of cytoplasmic miRNAs in gene silencing, nuclear-activating miRNAs (NamiRNAs) have been proposed to interact with enhancers and potentially activate gene transcription, representing an emerging mode of nuclear miRNA function that remains to be validated in diabetic systems. In this review, we summarize the current pathogenic mechanisms of hyperglycemia-induced metabolic memory and highlight both the established and emerging roles of miRNAs in epigenetic regulation within this field.