Long noncoding RNAs in insulin signaling: mechanisms, metabolic roles, and therapeutic prospects

Insulin signaling is a central regulator of metabolic homeostasis, controlling glucose uptake, lipid metabolism, protein synthesis, and pancreatic β-cell function. Dysregulation of this pathway contributes to insulin resistance, obesity, and type 2 diabetes mellitus (T2DM). Long noncoding RNAs (lncRNAs) have emerged as important regulators of gene expression and cellular signaling; however, their roles in modulating insulin signaling remain incompletely understood.

This review summarizes current advances in lncRNA-mediated regulation of insulin signaling and its implications in metabolic disease.

Recent studies examining the roles of lncRNAs in insulin signaling pathways were analyzed, with emphasis on tissue-specific functions and interactions with the insulin receptor/IRS/PI3K/Akt signaling axis.

lncRNAs regulate metabolic homeostasis in the liver, adipose tissue, skeletal muscle, and pancreatic β-cells by modulating insulin signaling, glucose transport, lipid metabolism, and β-cell function through transcriptional, post-transcriptional, epigenetic, and signaling mechanisms. Dysregulated lncRNA expression has been linked to insulin resistance and T2DM progression. Although transcriptomic studies have identified numerous insulin-responsive lncRNAs, mechanistic characterization and causal validation remain limited.

lncRNAs are critical modulators of insulin signaling and metabolic regulation. A deeper understanding of lncRNA-mediated regulatory networks may facilitate the identification of novel biomarkers and therapeutic targets for insulin resistance and T2DM.