microRNA-199a-5p mediates high glucose-induced reactive oxygen species production and apoptosis in INS-1 pancreatic β-cells by targeting SIRT1.
Hyperglycemia-induced pancreatic β-cell loss is a pathologic hallmark of type 2 diabetes mellitus (T2DM). This study was conducted to clarify the function of microRNA (miR)-199a-5p in high glucose-elicited β-cell toxicity and associated molecular mechanisms.



INS-1 rat pancreatic β-cells were cultured under normal (11 mM) or high (30 mM) glucose for 16-72 h and examined for miR-199a-5p expression. Gain and loss-of-function studies were performed to determine the role of miR-199a-5p in high glucose-induced apoptosis and reactive oxygen species (ROS) production. Additionally, the involvement of SIRT1 in the action of miR-199a-5p was checked.



High glucose caused a significant upregulation of miR-199a-5p in INS-1 cells compared to cells under normal glucose conditions. Pre-transfection with anti-miR-199a-5p inhibitors prevented the reduction in cell viability and inhibited ROS generation in INS-1 cells after high glucose treatment. In contrast, overexpression of miR-199a-5p significantly reduced cell viability and promoted apoptosis and ROS formation in INS-1 cells, which was coupled with a downregulation of SIRT1. Knockdown of SIRT1 led to apoptotic death in INS-1 cells. Moreover, enforced expression of SIRT1 blocked miR-199a-5p-induced ROS generation and attenuated high glucose-mediated apoptosis in INS-1 cells.



miR-199a-5p is upregulated in pancreatic β-cells in response to high glucose and promotes apoptosis and ROS generation by targeting SIRT1. The miR-199a-5p/SIRT1 axis may represent a promising target for the treatment of T2DM.
Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. HYKP890765@163.com.
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D000818:Animals; D017209:Apoptosis; D003924:Diabetes Mellitus, Type 2; D005947:Glucose; D035683:MicroRNAs / Q000235:genetics*; D051381:Rats; D017382:Reactive Oxygen Species; D056564:Sirtuin 1
D035683:MicroRNAs; D017382:Reactive Oxygen Species; C531408:mirn199 microRNA, human; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D005947:Glucose