Abstract
Background: Insulin resistance (IR) plays a pivotal role in the pathogenesis of type 2 diabetes, non-alcoholic fatty liver disease, and metabolic syndrome. Long non-coding RNAs (lncRNAs) have been recognized as important regulators of metabolic processes. This review examines the role of lncRNAs in the development and regulation of IR.
Methods: This structured narrative review was conducted through systematic searches in PubMed, Scopus, Web of Science, and Google Scholar databases (2010-2025). Keywords including "lncRNA," "insulin resistance," "glucose metabolism," "type 2 diabetes," and "ceRNA" were used with Boolean operators. Cellular, animal, and human studies related to the role of lncRNAs in IR were included. From 40 identified articles, relevant papers were selected for narrative analysis after screening.
Results: Various lncRNAs including MEG3, MALAT1, Reg1cp, XIST, H19, TUG1, SNHG12, and HEM2ATM showed different expression patterns in key tissues (liver, skeletal muscle, adipose tissue, and pancreas). These lncRNAs influence PI3K/AKT, FOXO1, SREBP, GLUT4, and Nrf2 signaling pathways through diverse mechanisms including acting as competing endogenous RNAs for miRNA sponging, protein interactions, and transcription factor regulation. Some lncRNAs such as MEG3 and MALAT1 were associated with IR exacerbation, while H19, TUG1, and SNHG12 showed protective roles.
Conclusions: Regulation of lncRNA expression through siRNA and antisense oligonucleotide technologies holds significant therapeutic potential for improving insulin sensitivity. Existing drugs such as metformin and resveratrol exert part of their effects through lncRNA modulation, and these molecules are emerging as therapeutic targets and diagnostic biomarkers.