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ludc web

Lena Eliasson

Principal investigator

ludc web

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

Author

  • Lisa Stoll
  • Adriana Rodríguez-Trejo
  • Claudiane Guay
  • Flora Brozzi
  • Mustafa Bilal Bayazit
  • Sonia Gattesco
  • Véronique Menoud
  • Jonathan Sobel
  • Ana Claudia Marques
  • Morten Trillingsgaard Venø
  • Jonathan Lou S. Esguerra
  • Mohammad Barghouth
  • Mara Suleiman
  • Lorella Marselli
  • Jørgen Kjems
  • Lena Eliasson
  • Erik Renström
  • Karim Bouzakri
  • Michel Pinget
  • Piero Marchetti
  • Romano Regazzi

Summary, in English

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.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes - Islet Patophysiology
  • NanoLund: Center for Nanoscience

Publishing year

2020

Language

English

Publication/Series

Nature Communications

Volume

11

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis
  • Diabetes - Islet Patophysiology

ISBN/ISSN/Other

  • ISSN: 2041-1723