Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing, China.
PLoS One. 2013 Jun 10;8(6):e64924. doi: 10.1371/journal.pone.0064924. Print 2013.
Insulin is known to regulate multiple cellular functions and is used for the treatment of diabetes. MicroRNAs have been demonstrated to be involved in many human diseases, including Type 2 diabetes. In this study, we showed that insulin decreased miR-99a expression levels, but induced glucose consumption and lactate production, and increased the expression of mTOR, HIF-1α and PKM2 in HepG2 and HL7702 cells. Forced expression of miR-99a or rapamycin treatment blocked insulin-induced PKM2 and HIF-1α expression, and glucose consumption and lactate production. Meanwhile, knockdown of HIF-1α inhibited PKM2 expression and insulin-induced glucose consumption. Taken together, these findings will reveal the role and mechanism of insulin in regulating glycolytic activities via miR-99a/mTOR.
胰岛素已知可调节多种细胞功能，并且被用于治疗糖尿病。已经证明 microRNAs 参与多种人类疾病，包括 2 型糖尿病。在这项研究中，我们表明胰岛素降低了 miR-99a 的表达水平，但诱导了葡萄糖消耗和乳酸生成，并增加了 HepG2 和 HL7702 细胞中 mTOR、HIF-1α 和 PKM2 的表达。强制表达 miR-99a 或雷帕霉素处理阻断了胰岛素诱导的 PKM2 和 HIF-1α 的表达，以及葡萄糖消耗和乳酸生成。同时，抑制 HIF-1α 抑制了 PKM2 表达和胰岛素诱导的葡萄糖消耗。总之，这些发现将揭示胰岛素通过 miR-99a/mTOR 调节糖酵解活性的作用和机制。
