A circular RNA generated from an intron of the insulin gene controls insulin secretion

Nat Commun. 2020 Nov 5;11(1):5611. doi: 10.1038/s41467-020-19381-w.


Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that insulin secretion is regulated by a circular RNA containing the lariat sequence of the second intron of the insulin gene. Silencing of this intronic circular RNA in pancreatic islets leads to a decrease in the expression of key components of the secretory machinery of β-cells, resulting in impaired glucose- or KCl-induced insulin release and calcium signaling. The effect of the circular RNA is exerted at the transcriptional level and involves an interaction with the RNA-binding protein TAR DNA-binding protein 43 kDa (TDP-43). The level of this circularized intron is reduced in the islets of rodent diabetes models and of type 2 diabetic patients, possibly explaining their impaired secretory capacity. The study of this and other circular RNAs helps understanding β-cell dysfunction under diabetes conditions, and the etiology of this common metabolic disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Gene Expression Regulation
  • Humans
  • Insulin / genetics*
  • Insulin / metabolism
  • Insulin Secretion / genetics*
  • Insulin-Secreting Cells / metabolism
  • Introns*
  • Mice
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Rats


  • DNA-Binding Proteins
  • Insulin
  • RNA, Circular
  • TARDBP protein, human