miR-7 regulates GLP-1 mediated insulin release by targeting β-arrestin 1

Glucagon-like peptide-1 (GLP-1) has been shown to potentiate glucose-stimulated insulin secretion binding GLP-1 receptor on pancreatic cells.-arrestin 1 ( ARR1) is known to regulate the desensitization of GLP-1 receptor. Mounting evidence indicates that microRNAs (miRNAs, miRs) are fundamental in the regulation of cell function and insulin release. However, the regulation of GLP-1/ ARR1pathways by miRs has never been explored. Our hypothesis is that specific miRs can modulate the GLP-1/ ARR1 axis in cells. To test this hypothesis, we applied a bioinformatic approachtodetectmiRsthatcouldtarget ARR1;weidentifiedhsa-miR-7-5p(miR-7)andwevalidated the specific interaction of this miR with ARR1. Then, we verified that GLP-1 was indeed able to regulate the transcription of miR-7 and ARR1, and that miR-7 significantly regulated GLP-1-induced insulin release and cyclic AMP (cAMP) production in cells. Taken together, our findings indicate, for the first time, that miR-7 plays a functional role in the regulation of GLP-1-mediated insulin release by targeting ARR1. These results have a decisive clinical impact given the importance of drugs modulating GLP-1 signaling in the treatment of patients with type 2 diabetes mellitus.