MicroRNA-125b-5p improves pancreatic β-cell function through inhibiting JNK signaling pathway by targeting DACT1 in mice with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a progressive disease, accompanied by increased insulin resistance and deteriorating beta-cell function. Previous studies have revealed that microRNA (miRNA) plays a crucial role in the treatment of T2DM. Hence, we aim to investigate the role of microRNA-125b-5p (miR-125b-5p) in pancreatic beta cell function and insulin sensitivity of mice with T2DM with the involvement of Dishevelled antagonist Dapperl (DACT1) and the c-Jun NH2-terminal kinases (JNK) signaling pathway. Firstly, a mouse model of T2DM was established by administering a high-fat diet plus low dosage of streptozotocin, and function of pancreatic beta-cell and insulin sensitivity in the normal and T2DM mice were detected. Then, the pancreatic beta-cells were collected from pancreatic islet tissues and treated with different mimics, inhibitors and siRNAs. After that, the relationship among miR-125b-5p, DACT1, and the JNK signaling-related factors in T2DM mice was determined. Finally, cell proliferation and apoptosis were determined. Mice with T2DM had lower pancreatic beta-cell function and insulin sensitivity, as well as diminished expression of miR-125b-5p but enhanced expressions of DACT1, JNK and c-Jun. miR-125b-5p inhibited DACT1 expression and the activation of the JNK signaling pathway, as well as restrained cell proliferation and promoted cell apoptosis. The current results suggest that up-regulated miR-125b-5p promotes insulin sensitivity and enhances pancreatic beta-cell function through inhibiting the JNK signaling pathway by negatively mediating DACT1.