MiR-184 expression is regulated by AMPK in pancreatic islets.
MiR-184 expression is regulated by AMPK in pancreatic islets.
复制标题
DOI：
10.1096/fj.201701100r
复制
发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Rutter GA
中科院分区：
文献类型：
--
作者：
Martinez-Sanchez A;Nguyen-Tu MS;Cebola I;Yavari A;Marchetti P;Piemonti L;de Koning E;Shapiro AMJ;Johnson P;Sakamoto K;Smith DM;Leclerc I;Ashrafian H;Ferrer J;Rutter GA
AMPK是一种重要的能量传感器，也是广泛应用的降糖药的靶点。在β细胞中，葡萄糖浓度升高会降低AMPK活性，并且两种催化亚基（β细胞特异性AMPK双敲除（β ampkdko）小鼠）的消融会损害体内胰岛素分泌和β细胞的特性。MicroRNAs （miRNAs）是一种小的rna，它沉默了对胰腺β细胞功能和特性至关重要的基因表达，并在糖尿病中发生改变。在这里，我们探索了小鼠和人β细胞中作用于AMPK下游的mirna。与对照组相比，我们在βAMPKdKO中发现了14个下调的mirna和9个上调的mirna。靶转录本的基因本体论分析揭示了β细胞功能和身份重要通路的富集。下调最多的miRNA是miR-184 (miR-184-3p)，它是β细胞功能和代偿扩张的重要调节因子，由葡萄糖控制，在糖尿病中减少。我们证明AMPK是葡萄糖对miR-184表达的负面影响的有效调节剂和重要介质。此外，我们揭示了miR-184在小鼠和人胰岛中的性别二态性表达。总之，这些数据表明葡萄糖介导的AMPK活性变化是胰岛中miR-184和其他mirna调控的核心，并在β细胞的能量状态和基因表达之间提供了联系。-Martinez-Sanchez， A.; Nguyen-Tu, m .；， 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.胰岛中MiR-184的表达受AMPK调控。
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.