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New Class of Genes Involved in Beta Cell Maturation and Diabetes

Researchers have identified a new class of genes that plays a role in maturation of pancreatic insulin‑producing beta (β) cells and may be involved in diabetes. RNA has been known historically as the intermediate between DNA and proteins: DNA is decoded into RNA, which in turn is translated into protein. However, recent research has discovered the 
presence of numerous RNA molecules that are encoded from DNA but not translated into proteins. A subset of these RNAs is called “long non‑coding RNAs” (lncRNAs), and their function is largely unknown, although research suggests that some may be involved in regulating whether genes are turned on or off (gene expression). While many protein‑coding RNAs are often present in several different cell types, lncRNAs are often found only in a single cell type. This observation 
suggests that lncRNAs may regulate cell‑speciic tasks, and potentially makes them attractive targets for therapy to affect one cell type. 

Because β cells are central to the development of both type 1 and type 2 diabetes, researchers sought to identify lncRNAs that were expressed in human pancreatic islets, which are primarily composed of β cells. They identiied over 1,100 lncRNAs expressed in islets, with about half of them expressed in islets only. They next looked at a subset of lncRNAs, to determine when they were expressed during β cell development. The lncRNAs were not present in early progenitor cells, but were active in mature islets, suggesting that they may play a role in promoting β cell maturation. Additional experiments suggested that lncRNAs may function by controlling the expression of islet‑speciic genes. These indings are important because a major goal of diabetes research is to identify strategies to turn progenitor cells into mature β cells, and this research has identiied a class of molecules that may be involved in this process and/or could be markers of mature β cells. 

The researchers next examined whether the lncRNAs may play a role in type 2 diabetes. They discovered a small number of lncRNAs that were abnormally expressed in human islets from people with type 2 diabetes, and others that were located near genetic regions previously shown to be associated with susceptibility to type 2 diabetes, suggesting that lncRNA abnormalities may explain part of the genetic susceptibility to type 2 diabetes. This research has therefore identiied a new class of genes that are expressed in islets, promote maturation of β cells, and may play a role in type 2 diabetes. It also opens up new avenues for studying and potentially promoting β cell maturation, and for examining the underlying genetic causes of diabetes toward identifying new targets for therapy.

Morán I, Akerman I, van de Bunt M, et al. Human β cell 
transcriptome analysis uncovers lncRNAs that are 
tissue‑speciic, dynamically regulated, and abnormally 
expressed in type 2 diabetes. Cell Metab 16: 435‑448, 2012.