INS and diabetes mellitus: Recent studies have suggested that newly identified circRNAs are novel factors in the initiation and development of IR.270 For example, ci-Ins2 is a conserved intronic circRNA derived from insulin pre-mRNA that exhibits lower levels in the islets of rodents and humans with type 2 diabetes.271 ci-Ins2 silencing in pancreatic islets leads to decreased expression of several genes important for insulin secretion (Rapgef4, Pld1, Pclo, and Cacna1c) by interacting with the TAR DNA-binding protein 43 (TDP43), thereby contributing to β-cell dysfunction during diabetes.