MiR‐184 expression is regulated by AMPK in pancreatic islets

AMPK is a critical energy sensor and target for widely used antidiabetic drugs. In β cells, elevated glucose concentrations lower AMPK activity, and the ablation of both catalytic subunits [β‐cell‐specific AMPK double‐knockout (βAMPKdKO) mice] impairs insulin secretion in vivo and β‐cell identity. MicroRNAs (miRNAs) are small RNAs that silence gene expression that are essential for pancreatic β‐cell function and identity and altered in diabetes. Here, we have explored the miRNAs acting downstream of AMPK in mouse and human β cells. We identified 14 down‐regulated and 9 up‐regulated miRNAs in βAMPKdKO vs. control islets. Gene ontology analysis of targeted transcripts revealed enrichment in pathways important for β‐cell function and identity. The most down‐regulated miRNA was miR‐184 (miR‐184–3p), an important regulator of β‐cell function and compensatory expansion that is controlled by glucose and reduced in diabetes. We demonstrate that AMPK is a potent regulator and an important mediator of the negative effects of glucose on miR‐184 expression. Additionally, we reveal sexual dimorphism in miR‐184 expression in mouse and human islets. Collectively, these data demonstrate that glucose‐mediated changes in AMPK activity are central for the regulation of miR‐184 and other miRNAs in islets and provide a link between energy status and gene expression in β cells.—Martinez‐Sanchez, A, Nguyen‐Tu, M.‐S., Cebola, I., Yavari, A, Marchetti, P., Piemonti, L., de Koning, E., Shapiro, A. M. J., Johnson, P., Sakamoto, K, Smith, D. M., Leclerc, I., Ashrafian, H., Ferrer, J., Rutter, G. A. MiR‐184 expression is regulated by AMPK in pancreatic islets. FASEB J. 32, 2587–2600 (2018). www.fasebj.org