MicroRNA-463-3p/ABCG4: A new axis in glucose-stimulated insulin secretion.
Glucose-stimulated insulin secretion (GSIS) is known to be essential in the control of metabolic fuel homeostasis, though the molecular mechanisms involved remain unclear.



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.



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.



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.
The Department of Human Anatomy of Jinzhou Medical University, Jinzhou, Liaoning, China.
Xuwei
X
Hou
School of Humanity and Management, Jinzhou Medical University, Jinzhou, Liaoning, China.
Wei
W
Wu
The Department of General Sugery, The First Affiliate Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
Bo
B
Yin
The Department of Human Anatomy of Jinzhou Medical University, Jinzhou, Liaoning, China.
Xuefeng
X
Liu
The Department of Human Anatomy of Jinzhou Medical University, Jinzhou, Liaoning, China. hxwily2015@sina.com.
Fu
F
Ren
D000070996:ATP Binding Cassette Transporter, Subfamily G / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D035683:MicroRNAs / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
C439766:ABCG4 protein, human; D000070996:ATP Binding Cassette Transporter, Subfamily G; D007328:Insulin; D035683:MicroRNAs; C000621252:microRNA463 microRNA, human; D005947:Glucose