Functions of circRNAs expressed in pancreatic β-cells. CircTulp4 [70], circAFF1, ciRS-7, circHIPK3 [33], and ci-Ins2 [73] are among the most abundant circRNAs expressed in pancreatic β-cells. CircTulp4, ciRS-7, and circHIPK3 are exonic circRNAs mainly localized in the cytoplasm and act as microRNA sponges. They affect the expression of different proteins involved in β-cell proliferation, insulin biosynthesis, and insulin secretion. CircAFF1 is also exonic and inhibits β-cell apoptosis through an unknown mechanism. Ci-Ins2 is an intronic circRNA localized mainly in the nucleus and interacts with the RNA-binding protein TDP-43. Ci-Ins2/TDP-43 interaction promotes the expression of many genes coding for proteins involved in insulin secretion. CircTulp4, ciRS-7, circHIPK3, and ci-Ins2 expression is downregulated in islets from db/db mice. Moreover, the level of ci-Ins2 is also decreased in the islets obtained from T2D patients.