MicroRNA-7a regulates pancreatic beta cell function

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Dysfunctional microRNA (miRNA) networks contribute to inappropriate responses following pathological stress and are the underlying cause of several disease conditions. In pancreatic beta cells, miRNAs have been largely unstudied and little is known about how specific miRNAs regulate glucose-stimulated insulin secretion (GSIS) or impact the adaptation of beta cell function to metabolic stress. In this study, we determined that miR-7 is a negative regulator of GSIS in beta cells. Using Mir7a2 deficient mice, we revealed that miR-7a2 regulates beta cell function by directly regulating genes that control late stages of insulin granule fusion with the plasma membrane and ternary SNARE complex activity. Transgenic mice overexpressing miR-7a in beta cells developed diabetes due to impaired insulin secretion and beta cell dedifferentiation. Interestingly, perturbation of miR-7a expression in beta cells did not affect proliferation and apoptosis, indicating that miR-7 is dispensable for the maintenance of endocrine beta cell mass. Furthermore, we found that miR-7a levels are decreased in obese/ diabetic mouse models and human islets from obese and moderately diabetic individuals with compensated beta cell function. Our results reveal an interconnecting miR-7 genomic circuit that regulates insulin granule exocytosis in pancreatic beta cells and support a role for miR-7 in the adaptation of pancreatic p cell function in obesity and type 2 diabetes.

Detaljer

Författare
  • Mathieu Latreille
  • Jean Hausser
  • Ina Stuetzer
  • Quan Zhang
  • Benoit Hastoy
  • Sofia Gargani
  • Julie Kerr-Conte
  • Francois Pattou
  • Mihaela Zavolan
  • Jonathan Esguerra
  • Lena Eliasson
  • Thomas Ruelicke
  • Patrik Rorsman
  • Markus Stoffel
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Endokrinologi och diabetes
Originalspråkengelska
Sidor (från-till)2722-2735
TidskriftJournal of Clinical Investigation
Volym124
Utgivningsnummer6
StatusPublished - 2014
PublikationskategoriForskning
Peer review utfördJa

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