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.