Investigating the role of microRNAs in insulin-secreting cells: focus on miR-9-5p, miR-101-3p and miR-187-3p

Insulin secretion from pancreatic β-cells is a key process in the regulation of blood glucose levels, and its impairment plays a major role in the development of type 2 diabetes (T2D). MicroRNAs (miRNAs) are small non-coding RNAs with regulatory functions. Preliminary high-throughput miRNA sequencing data revealed that several miRNAs are differentially expressed in human islets of Langerhans from nondiabetic (ND) and T2D donors. This study aimed at analyzing the role of three of these miRNAs (miR-9-5p, miR-101-3p and miR-187-3p) in the regulation of glucose-stimulated insulin secretion (GSIS). It was shown that overexpression (OE) of miR-101-3p increased GSIS in insulin-secreting INS-1 832/13 cells. Instead, neither its knockdown (KD), nor any change in the expression of the other two miRNAs, led to alterations in the secretion process. Expression levels of miR-9-5p and miR-187-3p were affected by increasing glucose concentration during 24-hour incubation, whereas all three miRNAs were influenced by palmitate. The increased GSIS after OE of miR-101-3p was confirmed in human insulin-secreting EndoC-βH1 cells. In conclusion, the data suggest that the upregulation of miR-101-3p, observed in islets from T2D donors, counteracts the activity of factors contributing to reduced GSIS during the development of T2D.