@article{10.1172/jci.insight.130521, author = {Rahul Agrawal AND Griffin Durupt AND Dinesh Verma AND Michael Montgomery AND Adriana Vieira-de Abreu AND Casey Taylor AND Sankar Swaminathan AND Simon J. Fisher}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {MicroRNA-7a overexpression in VMH restores the sympathoadrenal response to hypoglycemia}, year = {2019}, month = {11}, volume = {4}, url = {https://insight.jci.org/articles/view/130521}, abstract = {It is proposed that the impaired sympathoadrenal response to hypoglycemia induced by recurrent insulin-induced hypoglycemia (RH) is an adaptive phenomenon induced by specific changes in microRNA expression in the ventromedial hypothalamus (VMH). To test this hypothesis, genome-wide microRNAomic profiling of the VMH by RNA-sequencing was performed in control rats and rats treated for RH. Differential expression analysis identified microRNA-7a-5p and microRNA-665 as potential mediators of this phenomenon. To further test this hypothesis, experiments were conducted consisting of targeted lentiviral-mediated overexpression of microRNA-7a-5p and downregulation of microRNA-665 in the VMH. Hyperinsulinemic hypoglycemic clamp experiments demonstrated that targeted overexpression of microRNA-7a-5p (but not downregulation of microRNA-665) in the VMH of RH rats restored the epinephrine response to hypoglycemia. This restored response to hypoglycemia was associated with a restoration of GABAA receptor gene expression. Finally, a direct interaction of microRNA-7a-5p with the 3′-UTR of GABAA receptor α1-subunit (Gabra1) gene was demonstrated in a luciferase assay. These findings indicate that (a) the impaired sympathoadrenal response RH induces is associated with changes in VMH microRNA expression and (b) microRNA-7a-5p, possibly via direct downregulation of GABA receptor gene expression, may serve as a mediator of the altered sympathoadrenal response to hypoglycemia.}, number = {20}, doi = {10.1172/jci.insight.130521}, url = {https://doi.org/10.1172/jci.insight.130521}, }