Long Noncoding RNAs in Diabetes and beta-Cell Regulation

Diabetes is characterized by an insufficient physiological response to increases in blood glucose. There are two major types of diabetes: type 1 diabetes (T1D) and type 2 diabetes (T2D). T1D is the result of an immune-mediated destruction of the pancreatic beta cells, whereas T2D is characterized by reduced beta-cell function and insulin resistance. The incidence of both diabetes forms is increasing worldwide and has doubled since the 1980s. Long-term complications of diabetes include serious micro- and macro-vascular complications and an increased risk of premature death due to dysfunction and failure of various organs caused in part by the toxic effects of high blood glucose levels. In both forms of diabetes, genetic, epigenetic, and environmental factors contribute to the risk of developing the disease. Aberrant epigenetic modifications such as DNA methylation, histone modifications, and noncoding RNAs (ncRNAs) are well-recognized players in both T1D and T2D. Recent advances in chromosome conformation capture technologies have provided novel insights into the spatial arrangement of chromatin and have revealed the importance of beta-cell-specific lncRNAs in gene regulation and 3D chromatin folding in the beta cells. This chapter provides a comprehensive review covering lncRNAs in diabetes and their role in 3D chromatin architecture and beta-cell dysfunction and apoptosis.