Endocrine Abstracts

MicroRNAs are small noncoding RNA sequences that bind target mRNA and hinder protein translation. Studies have identified aberrant microRNA expression in type 2 diabetes (T2D), potentially reflecting a compensatory response or contributing to disease progression. Furthermore, microRNAs modulate islet and enteroendocrine peptides, and their respective receptors. TargetScan, miRDB and DIANA microT were used to predict microRNA targeting incretin receptor mRNA. Expression of hsa-miR-766-3p in islets and β-cells was gathered using miRmine. Publicly available islet and non-islet tissue RNAseq data were analysed to explore transcriptome-wide associations between hsa-miR-766-3p and other non-coding and coding RNA transcript abundances. RT-qPCR was utilised to investigate the expression of hsa-miR-766-3p in response to glucose in 1.4E7 human pancreatic beta cells, with further analysis exploring the effect of a hsa-miR-766-3p mimic on incretin receptor expression. The viability and proliferation of 1.4E7 cells post transfection was investigated using the MTT assay and cell count, respectively. Selected hsa-miR-766-3p was consistently predicted to target the GIPR with a strong predictive score (>80) and had evidenced expression in β-cells. In 1.4E7 cells, hsa-miR-766-3p expression was significantly altered in a high glucose environment (P < 0.05-0.01). Transient transfection with the hsa-miR-766-3p mimic demonstrated a marked increase in hsa-miR-766-3p expression; ⁷²hrs post transfection (P < 0.001), accompanied with reduced GLP-1R mRNA expression (P < 0.01) but no significant effect on GIPR expression. Transfection also significantly influenced cell viability (P < 0.05-P < 0.001) and proliferation (P < 0.01) in 1.4E7 cells. In summary, glucose responsive hsa-miR-766-3p regulates incretin receptor expression and modulates β-cell health, revealing its potential as a novel therapeutic target for T; ²D.