MicroRNA-463-3p/ABCG4: A new axis in glucose-stimulated insulin secretion

Obesity (Silver Spring). 2016 Nov;24(11):2368-2376. doi: 10.1002/oby.21655. Epub 2016 Sep 24.

Abstract

Objective: Glucose-stimulated insulin secretion (GSIS) is known to be essential in the control of metabolic fuel homeostasis, though the molecular mechanisms involved remain unclear.

Methods: MicroRNA (miRNA)-463-3p and ATP-binding cassette A4 (ABCG4) expression was analyzed by real-time PCR, and the potential role of miRNA-463-3p or ABCG4 was evaluated by overexpressing or silencing such miRNA or genes.

Results: The miRNA-463-3p inhibited GSIS without affecting cell viability. Further, mechanistic studies demonstrated that ABCG4 was a direct target of microRNA-463-3p and, to this effect, that ABCG4 played an important role in GSIS. The targeting was relevant in pancreatic islet β-cells, where GSIS through the miRNA-463-3p/ABCG4 axis was observed. Interestingly, in type 2 diabetes human pancreatic islets, expression of miRNA-463-3p and insulin was upregulated and ABCG4 downregulated compared with nondiabetic controls, and their expression levels were closely correlated.

Conclusions: The findings collectively establish a link between GSIS and the miRNA-463-3p/ABCG4 axis and represent a promising target for future diabetes mellitus treatments.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G / physiology*
  • Diabetes Mellitus, Type 2 / metabolism
  • Down-Regulation
  • Glucose / metabolism*
  • Humans
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • MicroRNAs / physiology*
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation

Substances

  • ABCG4 protein, human
  • ATP Binding Cassette Transporter, Subfamily G
  • Insulin
  • MicroRNAs
  • microRNA463 microRNA, human
  • Glucose