MicroRNA-463-3p/ABCG4: A New Axis in Glucose-Stimulated Insulin Secretion

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) 2463-3p 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 beta-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.