Long non-coding RNA-regulated pathways in pancreatic β cells: Their role in diabetes

Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that have not coding potential, but act as gene expression regulators through several molecular mechanisms. Several studies have identified tons of lncRNAs that are expressed in pancreatic β cells and many of them have been shown to have β cell-specific expression, suggesting a potential role in the regulation of basal β cell functions. Indeed, accumulating evidence based on numerous studies, has highlighted the implication of lncRNAs in the regulation of pancreatic β cell differentiation and proliferation, insulin synthesis and secretion, and apoptosis. In addition, several lncRNAs have shown to be implicated in pancreatic β cell dysfunction linked to different types of diabetes, including type 1 and type 2 diabetes, and monogenic forms of the disease. Pathogenic conditions linked to diabetes (inflammation or lipoglucotoxicity, for example) dysregulate the expression of several lncRNAs, suggesting that changes in lncRNA may alter potentially important pathways for β cell function, and eventually leading to β cell dysfunction and diabetes development. In this sense, functional characterization of some lncRNAs has demonstrated that these non-coding molecules participate in the regulation of several crucial pathways at the pancreatic β cell level, and dysregulation of these pathways leads to pathogenic phenotypes. In this review, we provide an overview of the action mechanisms of functionally characterized lncRNAs in healthy β cells and describe the contribution of some diabetes-associated lncRNAs to pancreatic β cell failure.